» Articles » PMID: 22272628

Alzheimer's Disease and Environmental Exposure to Lead: the Epidemiologic Evidence and Potential Role of Epigenetics

Overview
Specialty Neurology
Date 2012 Jan 26
PMID 22272628
Citations 55
Authors
Affiliations
Soon will be listed here.
Abstract

Several lines of evidence indicate that the etiology of late-onset Alzheimer's disease (LOAD) is complex, with significant contributions from both genes and environmental factors. Recent research suggests the importance of epigenetic mechanisms in defining the relationship between environmental exposures and LOAD. In epidemiologic studies of adults, cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition. In addition, research in animal models suggests a causal association between Pb exposure during early life, epigenetics, and LOAD. There are multiple challenges to human epidemiologic research evaluating the relationship between epigenetics, LOAD, and Pb exposure. Epidemiologic studies are not well-suited to accommodate the long latency period between exposures during early life and onset of Alzheimer's disease. There is also a lack of validated circulating epigenetics biomarkers and retrospective biomarkers of Pb exposure. Members of our research group have shown bone Pb is an accurate measurement of historical Pb exposure in adults, offering an avenue for future epidemiologic studies. However, this would not address the risk of LOAD attributable to early-life Pb exposures. Future studies that use a cohort design to measure both Pb exposure and validated epigenetic biomarkers of LOAD will be useful to clarify this important relationship.

Citing Articles

Massive changes in gene expression and their cause(s) can be a unifying principle in the pathobiology of Alzheimer's disease.

Coleman P, Delvaux E, Kordower J, Boehringer A, Huseby C Alzheimers Dement. 2025; 21(2):e14555.

PMID: 39912452 PMC: 11851168. DOI: 10.1002/alz.14555.


Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure.

Liu L, Emir U, Gu H, Sang L, Sawiak S, Cannon J Toxicol Sci. 2024; 202(1):123-141.

PMID: 39150886 PMC: 11514834. DOI: 10.1093/toxsci/kfae100.


Exposure to Lead in Drinking Water Causes Cognitive Impairment via an Alzheimer's Disease Gene-Dependent Mechanism in Adult Mice.

Kohler K, Macheda T, Hobbs M, Maisel M, Rodriguez A, Farris L J Alzheimers Dis. 2024; 100(s1):S291-S304.

PMID: 39121129 PMC: 11616619. DOI: 10.3233/JAD-240640.


Low-level Lead Exposure Impairs Fronto-executive Functions: A Call to Update the DSM-5 with Lead Poisoning as a Neurodevelopmental Disorder.

Neuwirth L, Lopez O, Schneider J, Markowitz M Psychol Neurosci. 2023; 13(3):299-325.

PMID: 37305358 PMC: 10254860. DOI: 10.1037/pne0000225.


Metals in Alzheimer's Disease.

Babic Leko M, Langer Horvat L, Spanic Popovacki E, Zubcic K, Hof P, Simic G Biomedicines. 2023; 11(4).

PMID: 37189779 PMC: 10136077. DOI: 10.3390/biomedicines11041161.


References
1.
Hu H, Tosteson T, Aufderheide A, WITTMERS L, Burger D, Milder F . Distribution of lead in human bone: I. Atomic absorption measurements. Basic Life Sci. 1990; 55:267-74. DOI: 10.1007/978-1-4613-1473-8_36. View

2.
von Lindern I, Spalinger S, Petroysan V, von Braun M . Assessing remedial effectiveness through the blood lead:soil/dust lead relationship at the Bunker Hill Superfund Site in the Silver Valley of Idaho. Sci Total Environ. 2003; 303(1-2):139-70. DOI: 10.1016/s0048-9697(02)00352-2. View

3.
Wang F, Hu H, Schwartz J, Weuve J, Spiro A, Sparrow D . Modifying effects of the HFE polymorphisms on the association between lead burden and cognitive decline. Environ Health Perspect. 2007; 115(8):1210-5. PMC: 1940090. DOI: 10.1289/ehp.9855. View

4.
Morris M . The role of nutrition in Alzheimer's disease: epidemiological evidence. Eur J Neurol. 2009; 16 Suppl 1:1-7. PMC: 3393525. DOI: 10.1111/j.1468-1331.2009.02735.x. View

5.
Hanson M, Godfrey K, Lillycrop K, Burdge G, Gluckman P . Developmental plasticity and developmental origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol. 2011; 106(1):272-80. DOI: 10.1016/j.pbiomolbio.2010.12.008. View