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Open access peer-reviewed chapter

The Role of Emerging Environmental Contaminants on Alzheimer’s Disease

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İ. İpek Boşgelmez and Beyza Mertaş

Submitted: 21 July 2025 Reviewed: 20 August 2025 Published: 08 October 2025

DOI: 10.5772/intechopen.1012558

Environmental Toxicology IntechOpen
Environmental Toxicology Understanding, Impact, and Mitigation Strateg... Edited by Suna Sabuncuoğlu and Onur Kenan Ulutaş

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Environmental Toxicology - Understanding, Impact, and Mitigation Strategies for a Sustainable Future

Suna Sabuncuoğlu and Onur Kenan Ulutaş

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Abstract

According to the latest data from WHO, about 57 million individuals worldwide were living with dementia in 2021, with 10 million new cases diagnosed each year. Alzheimer’s disease (AD) accounts for approximately 60–80% of dementia cases and ranks as the seventh leading cause of death globally. Currently, the therapeutic options available for AD have limited effectiveness, and potential disease-modifying therapies are not widely adopted or reliably deemed safe. Therefore, implementing preventive strategies and raising public awareness about the relevant AD risk factors are crucial. Existing data delineate various risk factors for AD, encompassing non-modifiable factors such as age, genetic predisposition, and gender, alongside modifiable factors including environmental pollution and diet. This chapter aims to explore emerging environmental risk factors that contribute to AD, including air pollution, toxic elements, pesticides, microplastics, nanoplastics, endocrine disruptors, pharmaceuticals and personal care products, environmental disasters, and global climate change. The intricate and multifaceted nature of neurodegenerative disorders such as AD necessitates an interdisciplinary approach to unravel the underlying mechanisms. This involves the effective application of various omics techniques—such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics—paired with advanced artificial intelligence (AI) methods, including machine learning and deep learning.

Keywords

  • Alzheimer’s disease
  • environmental risk factors
  • air pollution
  • water pollution
  • soil pollution
  • microplastics and nanoplastics
  • toxic metals
  • pesticides
  • pharmaceuticals and personal care products
  • changes to the natural environment
  • environmental disasters
  • global climate change
  • endocrine disruptors
  • noise pollution
  • light pollution

1. Introduction

Alzheimer’s disease (AD), first characterized by Dr. Alois Alzheimer in 1906, is a progressive neurodegenerative disorder marked by a progressive decline in cognitive functions and behavioral capabilities. It is recognized as the most common form of dementia and poses a growing challenge in the context of the aging global population. Currently, AD is an enduring and largely untreatable condition, with only a limited number of medications available, imposing a significant socio-economic burden [1, 2]. In 2021, AD and other dementias ranked as the seventh leading cause of mortality worldwide, accounting for approximately 1.8 million deaths. The mortality rate for AD is strongly correlated with aging (Figure 1a), particularly among individuals over 70 years of age [3]. Additionally, country-specific data highlight the global importance of this issue (Figure 1b). Furthermore, women are disproportionately impacted by dementia worldwide, comprising 68% of deaths related to AD and other dementias [4]. The hallmark features of AD include amyloid plaques—aggregates of amyloid-beta (Aβ) peptides—and neurofibrillary tangles, composed of hyperphosphorylated tau protein within the brain’s neural structures. This pathological protein aggregation disrupts the functions and communication of neuronal networks, thereby accelerating the cognitive decline typically observed in disease progression.

Figure 1.

(a) Mortality rate from AD and other dementias by age, (b) Global view of AD-related mortality across countries [3].

2. An overview of risk factors and hypotheses

As illustrated in Figure 2, risk factors related to AD are categorized into two groups: “non-modifiable factors,” such as genetics, gender, and aging; and “modifiable factors,” including lifestyle, various diseases, and environmental pollution. The key point is that these modifiable factors can be targeted to potentially prevent or delay up to 45% of dementia cases. Currently, these factors are categorized according to the stages of life, as early life, midlife, and late life risk factors [5]. The constantly evolving landscape of related AD research results in the daily emergence of new risk factors and updates in clinical practice.

Figure 2.

Risk factors and other key points of AD.

Various hypotheses related to AD (Figure 3), such as the amyloid, tau propagation, cholinergic, mitochondrial cascade, inflammatory, neurovascular, and metal ion hypotheses, have been proposed [6].

Figure 3.

Currently known hypotheses related to AD.

3. Neuroexposome and environmental risk factors

The term “exposome” refers to lifetime environmental exposures, including lifestyle factors, that begin prenatally [7]. Due to its variability and dynamism, precisely characterizing an individual’s exposure history is challenging. An “Alzheimer’s disease (AD) exposome” has been proposed to better understand environmental factors influencing genetic and non-genetic risks for AD and related dementias [8]. Figure 4 outlines the environmental risk factors currently recognized in this context.

Figure 4.

A representation of proposed environmental risk factors on neurodegenerative diseases.

3.1 Air pollution

Long-term air pollution exposure is linked to health risks, including cognitive decline, as studies clarify the harmful effects of specific pollutants. Airborne contaminants, such as particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2), may lead to impaired cognitive function, particularly in older adults. The data in Figure 5a [9] and 5b [3] show air pollutant emissions and average annual PM2.5 exposure, respectively, and offer a comprehensive overview of the global situation. Guo et al. reported a global rise in age-standardized mortality rates and disability-adjusted life years (DALYs) related to AD and other dementias, based on an analysis of ambient air pollution indicators—such as PM2.5, NO2, and O3—and covariates from 1990 to 2019 across 149 countries and territories [10].

Figure 5.

(a) air pollutant emissions [9], (b) average annual exposure to PM2.5 [3].

Over the past three decades, O3 levels increased annually by 0.17%, while PM2.5 and NO2 decreased by 0.33% and 0.14%, respectively. A 10 μg/m3 rise in PM2.5 was associated with a 0.118 (95% CI: 0.060–0.175) increase in ASMR and a 0.966 (95% CI: 0.321–1.611) increase in DALYs. Similarly, every 10 μg/m3 increase in O3 correlated with a 0.112 rise in ASMR and a 1.068 rise in DALYs. Notably, stronger associations between O3 and dementia were observed in the Global South compared to the Global North. Prolonged exposure to NO2 has been linked to lower memory and executive function assessment scores. Specifically, a significant decline of −0.10 in memory performance has been observed for each interquartile range increase [11].

Increased particulate matter exposure is associated with higher risks of cognitive decline, supported by odds ratios (OR: 1.49 for PM2.5; 1.30 for PM10) [12]. A recent systematic review [13] across Europe, Asia, and North America links PM2.5 and PM10 to behavioral issues in adults and the elderly, including olfactory dysfunction, cognitive deterioration, dementia, depression, and anxiety, with memory effects being most common. Some studies suggest gender-specific vulnerabilities, with women showing a higher incidence of adverse outcomes. Further research is needed to clarify the relationship between PM exposure and dementia risk.

Prolonged exposure to poor air quality is linked to neuroinflammation, immune response alterations, blood-brain barrier (BBB) disruption, and accumulation of Aβ-42 and α-synuclein, elevating risks of Alzheimer’s and Parkinson’s diseases, especially in APOE e4 allele carriers. This early-life exposure potentially heightens the risk of developing neurodegenerative diseases later in life [14].

Formaldehyde has also been implicated in the pathogenesis of neurodegenerative diseases due to its mechanism of action, which is significantly associated with heightened accumulation of Aβ. Exposure to exogenous formaldehyde may exacerbate this process in individuals who demonstrate a predisposition to Aβ accumulation, influenced by factors such as age or genetic traits. The receptor for advanced glycation end products (RAGE) is essential for the transport of Aβ across the BBB. The interaction of ligands with RAGE plays a crucial role in regulating the expression of the amyloid precursor protein (APP), a key component in the accumulation of Aβ. Endogenous formaldehyde accumulation within the body can result from impaired metabolic processes. In contrast, the accumulation of exogenous formaldehyde, which has been documented to surpass the maximum permissible concentration in various regions globally, may present more immediate and severe consequences [15]. Exposure to formaldehyde may lead to insulin deficiency, which impairs glucose metabolism and subsequently results in the accumulation of RAGE ligands, particularly advanced glycation end products (AGEs). The accumulation of glucose and the disruption of insulin-dependent biochemical signaling may trigger a cascade of reactions that promote neuroinflammation and various cellular disorders. Consequently, this increases the level of RAGE ligands in the system. The overexpression of RAGE at the BBB facilitates the transport of Aβ from the bloodstream into the brain. An increase in ligand-RAGE interactions subsequently upregulates the expression of the APP and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) genes, disrupting the equilibrium of APP processing and leading to the formation of elevated Aβ levels. The accumulation of Aβ contributes to the development of amyloid plaques. This phenomenon exhibits a cyclical nature; the deposition of amyloid plaques provokes neuroinflammation and diminishes neuroplasticity [15].

3.2 Water and soil pollution

Water pollution is a growing concern globally as the population and industrialization continue to rise. Contaminants detected in water sources include heavy metals such as lead (Pb), mercury (Hg), and arsenic (As), as well as pharmaceutical and cosmetic waste [16]. A study conducted in China found that an increase in water pollution resulted in worse mental health, with low-income participants being particularly vulnerable. Notably, the pollutants associated with adverse mental health outcomes were As, Hg, Pb, ammonia nitrogen (NH3-N), volatile phenol, and chemical oxygen demand (COD). Researchers also reported that water treatment ameliorated mental health by 0.12 percent [17]. It is also worth noting that water is the primary source of exposure to inorganic As. In Project FRONTIER, the association between the current and long-term As exposure and neuropsychological functioning was examined. The study included 434 participants, with a mean long-term As exposure of 240.15 μg/L-years over 34 years. The approximate current As level in the area where participants reside was 6.33 μg/L. Researchers have reported that long-term, low-level exposure to As is associated with impairments in global cognition, immediate memory, language, processing speed, and executive functioning [18]. Another study hypothesized that psychoactive pharmaceuticals from drinking water can cross maternal biological barriers and induce neurological disorders, including AD, by changing gene and protein expression [19]. In their previous study, Kaushik et al. [20] treated human neuronal cells with valproate and a mixture of fluoxetine, venlafaxine, and carbamazepine, and they found almost a 2-fold change in expression of genes associated with AD such as nuclear protein 1 (NUPR1), dihydropyrimidinase related protein 2 (DRP2), and Thrombospondin-1 (TSP1). NUPR1 is a gene that plays a role in cell apoptosis and regulation [21]. Both mixture and carbamazepine administration resulted in the upregulated expression of NUPR1, just as observed in AD patients [20]. Researchers suggest NUPR1 is related to brain damage [22], while Xu et al. found inhibition of NUPR1 improves learning and memory in vivo and reduces apoptosis [23]. Another downregulated gene in both AD and, due to the mixture and carbamazepine administration, is DRP2 [20, 24]. A current study found that DRP2 may be involved in regulating neuronal dedifferentiation during memory formation in complex conditioned tasks. This process appears to increase the pool of neuronal precursor cells, which can then differentiate in a targeted manner to encode newly acquired behaviors [25].

TSP-1 gene expression is downregulated in AD patients and in vivo models. One study indicates that Aβ reduces astrocytic TSP-1 secretion [26], while another suggests this gene offers protection against Aβ-induced mitochondrial fission, dysfunction, and apoptosis [27]. Taken together, these results indicate that mixtures of pharmaceutical waste in drinking water pose a significant risk factor for AD through multiple mechanisms. However, there are limited studies that investigate the association between pharmaceutical waste and AD. More demographic studies are crucial for taking effective measures and analyzing levels of heavy metals, especially As, as well as cosmetic and pharmaceutical waste, in drinking water.

The Food and Agriculture Organization of the United Nations (FAO) defines soil pollution as “the presence in the soil of a chemical or substance out of place and/or present at a higher than normal concentration that has adverse effects on any non-targeted organism” [28]. According to the FAO, several sources contribute to soil pollution, including pesticides, plastic and healthcare waste, naturally occurring asbestos, organic contaminants, transportation, and trace elements [29]. Li et al. found that soil As concentration was significantly associated with AD mortality rates, whereas no such association was observed for Pb, Cd, and Hg. The researchers noted the lack of investigation into As levels in drinking water as a limitation and emphasized the necessity of incorporating water exposure assessments in future studies on As and AD prevalence, given the potential for metal exchange between soil and water [30]. An analysis of data from all 48 US states examined the correlation between AD mortality rates and 41 trace elements. Results showed that soil selenium levels had the strongest inverse relationship with AD mortality rates, while soil tin concentrations were most notably linked to a decrease in AD mortality growth, followed by sulfur. The study also posited that selenium and sulfur levels in soil could account for approximately 20.8% of the observed spatial variation in AD mortality across these states [31]. Overall, these results suggest that soil composition can be both a risk and a protective factor. Studies examining specific trace elements and their association with AD could help determine beneficial components and improve soil quality. Furthermore, increasing public awareness and promoting effective agricultural practices can serve as a long-term and effective intervention.

3.3 Noise and light pollution

Alongside air pollution, noise pollution—such as traffic noise and around-the-clock noise at work—has become a significant public health concern. Noise pollution is an emerging health threat globally, affecting approximately 132 million people in Europe. According to the European Environment Agency, more than 30% of Europeans are exposed to noise levels known to increase the risk of cardiovascular, metabolic, and mental health diseases [32]. Noise can increase the risk of both auditory and non-auditory health conditions, including cardiovascular diseases, diabetes, and cognitive/neurodegenerative disorders [33, 34]. Specific occupational and routine environments may expose individuals to prolonged noise, potentially leading to emotional and cognitive problems linked to neurobiological changes resembling those seen in AD. Growing research in epidemiology and experimental studies underscores the connection between ongoing noise exposure and declining cognitive function. When exposed to noise, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system are activated, resulting in the secretion of stress hormones, including catecholamines and cortisol. Chronic noise exposure precipitates sustained inflammation and oxidative damage, which may contribute to various health issues. This underscores the importance of mitigating noise pollution to protect public health. Furthermore, the roles of inflammation and oxidative stress in noise-induced vascular dysfunction, circadian rhythm disturbances, accelerated aging, neuroinflammation, and alterations in the microbiome are significant, emphasizing their interconnected nature [35].

In a rat model of chronic noise-induced cognitive impairment [36], the pathological condition of the hippocampus and levels of ferroptosis were examined using Western blotting and immunohistochemical techniques. Subsequent bioinformatics analysis identified several key genes, including the retinoic acid receptor responder-2 gene, which has been proposed as a protective factor in AD. This gene, acting upstream of ferroptosis, was suggested as a potential target for preventing and treating noise-induced cognitive impairment. In another study examining the molecular mechanisms behind cognitive impairment induced by continuous noise exposure, researchers found decreased expression of the serum/glucocorticoid-regulated kinase 1 (SGK1) gene and its associated protein. This dysregulation inhibited the intracellular PI3K/SGK1/Foxo3 pathway, resulting in increased expression of apoptotic proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Fas Ligand (FasL), and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) [37]. However, considering the intricate interplay of various risk factors, further data are essential to clarify the causal relationship between noise pollution and neurodegenerative diseases [38].

3.4 Examples of known and emerging toxicants

3.4.1 Endocrine disruptors

According to WHO [39], “An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, its progeny, or (sub)populations.” Whether synthetic or natural in origin, their action involves mimicking or blocking the actions of endogenous hormones. A meta-analysis of studies involving 286,610 participants identified endocrine-disrupting chemicals (EDCs) as significant risk factors for neurodegenerative diseases, with high exposure to EDC mixtures associated with a 1.03-fold increased risk of AD. A positive correlation between AD risk and polychlorinated biphenyls (PCBs) was also reported [40]. A study found that prenatal BPA exposure alters gene expression in offspring’s hippocampus, affecting 1633 genes in males and 2780 in females compared to controls. These genes are involved in inflammation, synaptic transmission, neuritogenesis, and neurodevelopment, and are associated with AD and related neurological disorders such as cognitive impairment and tauopathies. BPA exposure also increased nuclear factor-κB (NF-κB) levels exclusively in males, indicating sex-specific pathways. It also differentially affected BACE1 expression—upregulating it in males with no change in females—suggesting sex-dependent effects on amyloid processing [41].

Taken together, these findings underscore the need to consider sex differences and prenatal exposure when investigating the association between AD and EDCs. Exposure to EDCs begins prenatally and continues throughout life; thus, their cumulative effects on AD must be considered and investigated. Therefore, more epidemiological and in vivo studies are crucial not only to improve regulatory policies regarding these pollutants but also to make effective interventions to raise public awareness.

3.4.2 Pesticides

The rise in the global population and the growing need for food and pest management have resulted in extensive pesticide use, raising awareness of the potential link between pesticides and AD. In particular, the association between prolonged exposure to low doses of pesticides and AD, as well as other neurodegenerative disorders, has garnered significant attention. A meta-analysis of seven studies reported an OR of 1.34 (95% CI: 1.08–1.67), supporting the hypothesis that pesticides could be a risk factor for AD [42]. A significant positive correlation between pesticide exposure and AD was observed in high-use regions in Spain, with an OR of 2.09 compared to lower-exposure areas. Female subjects exhibited a higher risk (OR: 2.27), suggesting gender-specific susceptibility to pesticide neurotoxicity. These findings highlight the importance of incorporating gender considerations in research and public health policies targeting environmental neurodegenerative risks [43]. Hayden et al. [44] reported that after adjusting for baseline age, gender, education, APOE ε4 status, and baseline Modified Mini-Mental State Examination scores (MMSE), Cox proportional hazards (CPH) models indicated increased risks among pesticide-exposed individuals for all-cause dementia (HR 1.38, 95% CI 1.09–1.76) and for AD (HR 1.42, 95% CI 1.06–1.91). The risk of AD associated with exposure to organophosphates (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.05–2.23) was slightly higher than that linked to organochlorines (HR 1.49, 95% CI 0.99–2.24), which was nearly statistically significant. In a CPH study of 26 agricultural activities, increased AD risk correlated with high pesticide use. The hazard ratios were higher in crop farming, fruit arboriculture, and viticulture [3.72 (95% CI: 3.47–3.98), 1.36 (1.15–1.62), and 1.29 (1.18–1.42), respectively], while lower risks were observed among breeders [45].

Despite bans over 50 years ago due to environmental persistence, the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite, dichlorodiphenyldichloroethylene (DDE), are still detectable in some countries, pointing to ongoing concerns. Both compounds elevate APP levels in human neuroblastoma cells, reinforcing a mechanistic connection. Elevated serum DDE is significantly associated with a 3.8-fold increased risk of AD, with a correlation coefficient of 0.95 between serum and brain DDE levels. Specifically, within the subgroup exposed to the highest tertile of DDE, carriers of the APOE ε4 allele scored approximately 1.75 points lower on the MMSE compared to those with the APOE ε3 allele. In this context, detecting individuals with high levels of DDE and carrying an APOE ε4 allele may enable early identification of some AD cases [46]. Further mechanistic investigations revealed that exposure to DDT significantly upregulated APP mRNA and protein levels in SH-SY5Y cells, primary neuronal cultures, and both wild-type (C57BL/6J) and 3xTG-AD mouse models. An increase in secreted Aβ levels was also detected in SH-SY5Y cells, with this effect being counteracted by the sodium channel blocker tetrodotoxin. Transgenic flies and 3xTG-AD mice exhibited heightened Aβ pathology following DDT exposure, indicating a possible link between DDT and Aβ-aggregation. Moreover, levels of synaptic markers such as synaptophysin and PSD95 were decreased in the cortices of 3xTG-AD mice [47].

Bartholomew et al. [48] reported that administration of glyphosate to 3xTg-AD mice resulted in decreased survival rates, increased thigmotaxis in the Morris water maze, and significant elevations in the enzyme BACE1, which is involved in amyloidogenic processing. Additionally, there was an increase in insoluble Aβ-42 fractions, greater plaque load and enlarged plaques, as well as elevated levels of pTau at epitopes Threonine 181, Serine 396, and the AT8 epitope (Serine 202, Threonine 205). Pro- and anti-inflammatory cytokines and chemokines increased and persisted in the brain tissue of both 3xTg-AD and non-Tg groups, as well as in the peripheral blood plasma of 3xTg-AD. Additionally, the primary metabolite of glyphosate, aminomethylphosphonic acid, was detected in the brains of 3xTg-AD and non-Tg mice exposed to glyphosate, even after a 6-month recovery period.

Recent in vitro research [49] suggests that pyrimethanil, a fungicide, accelerates Aβ42 aggregation by promoting the formation of small oligomers during the lag phase and inducing β-sheet-structured aggregates. In the presence of preformed seeds, pyrimethanil has a dual role, fragmenting fibrils and promoting aggregation, likely through interactions with smaller seeds. Pyrimethanil shows a higher affinity for fibrils than for monomers, thereby weakening the interactions between monomers and fibrils.

3.4.3 Toxic metals and other elements

Various elements such as aluminum (Al), arsenic (As), iron (Fe), manganese (Mn), lead (Pb), copper (Cu), and cadmium (Cd) have garnered academic interest in this context [50, 51, 52, 53]. Some of these metals have been proposed to interfere with key neural processes, including oxidative stress regulation, mitochondrial function, and autophagy, promoting neurodegeneration. Specifically, it has been posited that As influences tau phosphorylation and Aβ accumulation; Mn affects glutamate regulation and excitotoxicity; and Pb and Cd impair mitochondrial bioenergetics and induce cellular senescence, elucidating their roles in AD pathogenesis [52].

3.4.4 Microplastics and nanoplastics

Given the extensive utilization of plastics across various sectors—including food and beverage packaging, pharmaceuticals, dietary supplements, infant feeding bottles, and medical devices—exposure to plastic materials in everyday life has become nearly unavoidable. Considering that human exposure to plastics begins prenatally, it is essential to examine the degree of bioaccumulation within the human body, as well as its distribution patterns and the overall fate. A recent post-mortem study found that brain concentrations of micro- and nanoplastics (MNPs) are 7–30 times greater than in the liver and kidney. Furthermore, brain samples from decedents in 2024 showed approximately 50% higher concentrations of MNPs compared to those from 2016. Markedly increased levels of MNPs were detected in the brain tissues of individuals diagnosed with dementia, with further accumulation observed in cerebrovascular walls and immune cells. Researchers have emphasized that a comprehensive understanding of the pathways of exposure, absorption, and elimination of MNPs, as well as their potential harmful effects—especially on the brain—is essential [54].

A recent study investigated the effects of prenatal nano-plastic exposure and found that nano-polystyrene-exposed rats’ offspring exhibited upregulation of pregnancy-zone protein (PZP), fibronectin 1 (FN1), and alpha-2-macroglobulin (α-2 M) in the hippocampus. Researchers suggested that these changes suggest potential neural damage in the experimental group. They also found downregulation of kinesin family member 21A (KIF21A), stathmin (STMN2), dematin actin-binding protein (DMTN), and MAGUK scaffold protein discs large (DLG1) in the nano-polystyrene-exposed rats’ offspring. They hypothesized that the downregulation of DMTN increased the risk of brain tumors, while the downregulation of STMN2 and KIF21A was associated with impaired synaptic development in offspring. Additionally, they observed downregulation of DLG1, which plays a key role in neuronal development and synaptic regulation in offspring. Given this, the results suggest prenatal exposure to nanoplastics (NPs) represents a neurodevelopmental risk factor through several proteins linked to neural and synaptic development and functions [55]. Another study administered an environmentally relevant dose (10 mg/kg/day) of NPs to APP/PS1 mice for 28 days and reported that NPs significantly elevated the number and varying sizes of Aβ plaques. Additionally, they found that NPs impair cellular responses by decreasing the number and activation of microglia and astrocytes and suggested that NPs exposure might exacerbate AD progression.

Researchers hypothesize that microglia are the primary cells mediating dose-dependent NP uptake in the AD brain, providing insight into AD pathology [56]. Concurrently, co-exposure to ozone and polystyrene induces anxiety-like behaviors, cognitive deficits, and neuronal and BBB damage. This exposure elevates neuroinflammation, evidenced by increased pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and reduced anti-inflammatory factors (TGF-β, YM-1, and IL-10). It also enhances pyroptosis markers (caspase-1, GSDMD-N, IL-18, and IL-1β) and exacerbates oxidative stress, indicated by decreased superoxide dismutase (SOD) and increased 4-hydroxynonenal. Notably, exposure to either pollutant alone yielded minimal effects. These findings suggest synergistic interactions between NPs and air pollutants in promoting AD onset and progression [57].

Bashirova et al. examined the impact of nanoparticle size (50 and 140 nm) and concentration (0, 10, 50, and 100 ppm) of polyethylene terephthalate (PET) on Aβ1-40 fibrillation. The findings indicate that PET50nm accelerates fibrillation more than PET140nm across all concentrations. Fibrillation time increases with concentration but levels off at higher amounts. PET NPs at 50 nm and 100 ppm promote Aβ aggregation by enhancing fibril growth and nucleation [58].

3.4.5 Pharmaceuticals and personal care products

Pharmaceutical products and their metabolites, specifically non-steroidal anti-inflammatory drugs (NSAIDs), beta-blockers, hormones, antidepressants, and antiepileptics, are frequently detected in the environment [59]. These substances may be regarded as emerging risk factors for AD. According to the WHO, one of the main limitations when assessing the hazardous effects of waste pharmaceuticals is that very few studies and monitoring programs are available [60]. Moreover, pharmaceutical waste profiles differ internationally in both quantity and quality. Further research is required to evaluate how changes in pharmaceutical waste composition affect public health and to pinpoint at-risk groups. Nonetheless, it is reasonable to assume that as the population ages and pollution rises, pharmaceutical use and waste are expected to increase. Monitoring pharmaceutical waste, implementing preventive strategies, and enhancing public awareness are critical measures to mitigate its potential hazards effectively.

Personal care products constitute an emerging environmental risk factor, accumulating gradually over time. The most prevalent among these are fragrances, UV filters in sunscreens, chemicals in hair dyes, preservatives, insect repellents, and bactericidal/disinfectant agents [61]. Studies have documented the ubiquitous presence of pharmaceuticals and personal care products (PPCPs) across various water resources, including surface water, groundwater, wastewater, drinking water, and oceans; a typical example is triclosan [62]. The widespread production and consumption of PPCPs have led to an increase in their release into the environment. If adequate measures are not taken to control their environmental release, their potential adverse effects on public health are likely to become more pronounced over time. These adverse effects might be attributed to their specific mechanisms of action or to certain excipients included in the formulation.

A recent study [63] investigated the association between cognitive function and exposure to phenols, parabens, and phthalates widely used in cosmetic ingredients. In total, nine compounds across various categories were included in the analysis: BPA and triclosan (TCS) as phenolics; methylparaben (MPB) and ethylparaben (EPB) as parabens; and mono-2-ethyl-5-carboxypentyl phthalate (MECP), mono-ethyl phthalate (MEOH), mono-2-ethylhexyl phthalate (MEHP), mono-isobutyl phthalate (MiBP), and mono-benzyl phthalate (MBzP) as phthalates. The findings indicate a significant correlation with cognitive impairment for each of the nine exposures. Researchers emphasized that the cognitive function of the male population is more affected by the compounds examined in the study. Among all the compounds, MECP exposure was found to have the most significant influence [63]. An AD model in Caenorhabditis elegans revealed that early-life and prolonged exposure to di(2-ethylhexyl) phthalate (DEHP), the second most frequently identified phthalate in cosmetic products, increases intracellular reactive oxygen species (ROS) levels and Aβ deposition [64, 65]. DEHP has been shown to upregulate bec-1, which is associated with apoptosis and autophagy and causes apoptotic cell death when activated [64, 66]. They also hypothesized that upregulation of bec-1 leads to increased accumulation of lysosome-related organelles (LROs) through Aβ-induced autophagosome formation, emphasizing the significance of the autophagy–lysosomal degradation pathway in response to DEHP exposure [64].

In addition to phthalates, exposure to heavy metals via personal care products may constitute a significant risk factor for AD. Notably, aluminum—an element extensively found in cosmetics, including eye shadows, mascaras, lipsticks, and antiperspirants—raises particular concern due to its pervasive presence [67]. Even though several studies have shown a relationship between aluminum exposure and AD, there is insufficient evidence to conclusively establish a link between aluminum exposure from personal care products and the development or progression of the disease [68, 69]. In the study by Rusina et al. [70], the mean aluminum concentration in the brains of AD patients was approximately four times higher than that of healthy controls. A post-mortem study with familial AD patients detected co-localization of aluminum and neurofibrillary tangles in their frontal cortex, temporal, and parietal lobes [68]. Another study investigated aluminum-regulated mechanisms, resulting in abnormal tau phosphorylation, and hypothesized that aluminum can modulate tau hyperphosphorylation via protein kinases and phosphatases that take part in the phosphorylation and production of the tau protein, such as glycogen synthase kinase 3 beta (GSK-3β) and PP2A. They also found that aluminum influences ubiquitin-proteasome pathway (UPP), which modulates tau hyperphosphorylation by selectively recognizing and degrading misfolded and aggregated tau proteins. In that study, aluminum doses specifically correlated with phosphorylated tau proteins such as pThr181, pThr231, and pSer396 [69]. Furthermore, a study shows that aluminum is cytotoxic and promotes oxidative stress, with Aβ42 significantly amplifying these effects, nearly doubling ROS-positive cells. These findings suggest aluminum’s role in AD, likely through oxidative stress and cytotoxicity, and highlight its synergistic interaction with Aβ [71]. Taken together, the literature suggests that aluminum may be a risk factor for AD, acting through multiple mechanisms, influencing tau hyperphosphorylation via GSK-3β, UPP, and protein phosphatase 2A (PP2A), as well as inducing oxidative stress and cell death alongside Aβ42 [69, 71]. Although some excipients used in PPCPs are associated with causing disease onset and exacerbating prognosis, it remains unclear whether the concentrations in these products are sufficient to exert such effects, emphasizing the need for further studies in this area.

3.5 Changes to the natural environment

3.5.1 Global climate change

Recent studies revealed a potential link between climate change and the increased incidence of neurodegenerative diseases, including AD [72, 73]. Wei et al. [73] found that a 1.5°C increase in the summer mean temperature was associated with a 12% increase in dementia-related hospital admissions [72]. In line with these findings, Culqui et al. (2017) reported that when the maximum daily temperature surpassed the 34°C heatwave threshold, emergency hospital admissions for AD increased by 23.1%, with this association observed exclusively for temperatures exceeding this threshold [74]. A recent study emphasizes the growing threat of extreme heat to older adults living with AD and related dementias. The study indicates that higher temperatures significantly increase hospital admissions for AD and related dementias, with researchers urging clinicians and policymakers to address the risks of extreme heat for individuals with dementia and raise public awareness [75]. Another study found a marked increase in mortality due to AD and other forms of dementia during and after heatwave events. Researchers have underscored the urgent need for targeted public health interventions for AD and other dementia patients, noting that the implementation of appropriate heatwave response policies could significantly reduce heat-related mortality [76]. A study conducted in the United Kingdom estimated that each 1°C increase in high temperature is associated with a 4.5% rise in dementia-related hospital admissions. Also in the study, researchers considered two potential future emissions scenarios: a low emissions scenario, in which global greenhouse gas (GHG) emissions are significantly reduced under a firm global mitigation policy, and a high emissions scenario, where GHG emissions continue to rise with minimal mitigation efforts, alongside increasing wealth and population. In the high emissions scenario, they predicted a 194% increase in 2030 and a 294% increase in 2040, corresponding to approximately 360 admissions in 2030 and 482 admissions in 2040, compared to 122 admissions in 2009. In the low emissions scenario, heat-attributable hospital admissions were predicted to rise by 214% in 2030 and 263% in 2040. In absolute numbers, this equates to approximately 357 heat-related admissions in 2030 and 412 admissions in 2040, compared to 114 in 2009 [77]. Although several studies suggest a link between climate change and AD, the mechanisms behind this association remain unclear. One potential mechanistic pathway through which climate change may influence the onset or progression of AD is mediated by age-related physiological changes that impair thermoregulatory efficiency. As a result of decreased basal metabolic rate, reduced muscle mass, and altered vasoconstrictor responses, older adults exhibit increased sensitivity to temperature variations and a diminished capacity for thermoregulatory adaptation [78, 79]. Another potential mechanism concerns the substantial anatomical overlap between specific brain regions involved in altered thermal perception and social cognition. This anatomical convergence suggests that thermoregulatory homeostasis may be impaired in mental diseases, which could help explain the increased sensitivity of individuals with dementia to climate change [80].

3.5.2 Environmental disasters and related loss

Environmental disasters are multidimensional risk factors for AD as they include psychological and physical trauma, heightened stress, loss of relatives and friends, financial loss, and migration. A meta-analysis reported that natural disasters significantly increase the risk of AD, all-cause dementia, and cognitive decline. Researchers emphasized that hurricanes, heat waves, and earthquakes with tsunamis are associated with a heightened risk of dementia and cognitive decline compared to other natural disasters, and they attributed this increased risk to their varying combinations of physical, psychological, and social factors [81].

A study investigated dementia risk after the 2011 Great East Japan Earthquake and tsunami and found that the loss of housing is significantly associated with a three-year decline in cognitive performance, and disasters exacerbate dementia symptoms. Researchers highlighted that depression onset and deteriorated social relationships might be potential mechanisms linking cognitive decline with the loss of housing. Interestingly, there was no significant association reported between dementia and the loss of relatives or friends [82]. However, another study conducted in Utah found that participants who faced three or more deaths of family members during adulthood, which might occur due to natural disasters, had double the risk of developing AD [83]. Every element and combination of the aftermath of disasters represents a risk factor whose significance might vary individually. When studying the link between AD and natural disasters, it is crucial to recognize these consequences as key risk factors and create supportive environments for affected individuals. The findings highlight the importance of exploring how environmental disasters influence diseases across various cultures and regions. More global research is needed to better understand the geographic, regional, and cultural factors involved.

Considering AD within the framework of natural disasters is essential, as both patients and caregivers encounter distinct challenges in these circumstances. A study reported that 96.3% of caregivers of AD and related dementia patients expressed a need for additional information on emergency planning. During disaster evacuations, caregivers reported challenges related to stigma and privacy, which may exacerbate patients’ behavioral symptoms [84]. Given this, raising public awareness and organizing educational training programs for emergencies and disasters could benefit patients, families, and caregivers alike. Additionally, environmental hazards, such as unanticipated pollutant exposures, further complicate such scenarios.

4. Conclusion and future perspectives

In view of the complex nature of neurodegenerative diseases, including AD, a growing list of disciplines in addition to neurology, epidemiology, public health, and gerontology have started to contribute to the field. It is widely accepted that investigating novel biomarkers and drug targets is crucial for advancing the prevention and treatment of AD. While the APOE ε4 allele is a primary genetic risk factor for AD, recent research indicates its association with Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Additionally, a five-protein panel—SPC25, NEFL, S100A13, TBCA, and LRRN1—has been identified as a predictor of APOE ε4 status independently of clinical diagnoses [85]. Therefore, in addition to the aforementioned disciplines, a number of related fields, including, but not limited to, toxicology, pharmacology, and ecology, should take part in well-designed, controlled studies to shed light in the sources of exposure, specific mechanisms as well as interrelationship between the potential mechanisms, exposure models and other required points that remain to be fully elucidated. In this context, realizing AI’s promise in AD research requires concerted efforts across diverse sectors and fields. Harnessing AI’s full potential in AD research—such as developing non-invasive digital biomarkers, exposure monitoring via wearable sensors, early detection, patient stratification, and enhanced clinical trial efficiency—necessitates multidisciplinary collaboration [86].

Conflict of interest

The authors declare no conflict of interest.

Notes/thanks/other declarations

The authors express their gratitude to all researchers involved in AD studies, along with the patients and their families, for their essential contributions in investigating risk factors and exploring new treatments. The authors apologize to colleagues whose work cannot be cited due to space constraints.

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Written By

İ. İpek Boşgelmez and Beyza Mertaş

Submitted: 21 July 2025 Reviewed: 20 August 2025 Published: 08 October 2025

© 2025 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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