Epigenetics, oxidative stress, and Alzheimer disease

Topic: Amyloid, tau and blood-test diagnosis

Alzheimer disease (AD) is a progressive neurodegenerative disorder whose clinical manifestations appear in old age. The sporadic nature of 90% of AD cases, the differential susceptibility to and course of the illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late-onset AD. Animal exposure studies demonstrated that AD may begin early in life and may involve an interplay between the environment, epigenetics, and oxidative stress.

@article{zawia2009-19245828,
  author  = {Zawia, N. H. and Lahiri, D. K. and Cardozo-Pelaez, F.},
  title   = {{Epigenetics, oxidative stress, and Alzheimer disease}},
  journal = {Free radical biology \& medicine},
  year    = {2009},
  doi     = {10.1016/j.freeradbiomed.2009.02.006},
  pmid    = {19245828},
  url     = {https://doi.org/10.1016/j.freeradbiomed.2009.02.006}
}

Key findings

• The sporadic nature of 90% of AD cases, the differential susceptibility to and course of the illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late-onset AD.
• Animal exposure studies demonstrated that AD may begin early in life and may involve an interplay between the environment, epigenetics, and oxidative stress.
• Early life exposure of rodents and primates to the xenobiotic metal lead (Pb) enhanced the expression of genes associated with AD, repressed the expression of others, and increased the burden of oxidative DNA damage in the aged brain.
• Epigenetic mechanisms that control gene expression and promote the accumulation of oxidative DNA damage are mediated through alterations in the methylation or oxidation of CpG dinucleotides.

Why it matters

This review discusses evidence that epigenetic and environmental factors, including early-life exposure to lead, may contribute to late-onset Alzheimer's disease along with oxidative stress. It is a review and does not report a proven treatment, cure or prevention.

New to this subject? Start with our plain-English guide: Genetics →

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.freeradbiomed.2009.02.006
• PubMed: 19245828
• Original source →
• Free full text: PubMed Central →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science (New York, N.Y.) · 1987-02-01 · usefulness score 57/100 · Down syndrome and Alzheimer's
• Amyloid plaque core protein in Alzheimer disease and Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1985-06-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochemical and Biophysical Research Communications · 1984-05-01 · usefulness score 54/100 · Disease mechanisms
• Heritability for Alzheimer's disease: the study of dementia in Swedish twins The journals of gerontology. Series A, Biological sciences and medical sciences · 1997-03-01 · usefulness score 51/100 · Brain tissue and pathology
• ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein The Journal of biological chemistry · 2006-04-19 · usefulness score 47/100 · Risk genes beyond APOE
• Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides Proceedings of the National Academy of Sciences of the United States of America · 1987-06-01 · usefulness score 45/100 · Down syndrome and Alzheimer's
• S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production Molecular and cellular neurosciences · 2005-01-01 · usefulness score 44/100 · Risk genes beyond APOE

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• Neurodegenerative and neurological disorders by small inhaled particles Neurotoxicology · 2016-07-19 · usefulness score 47/100 · Inflammation and the immune system
• Genome instability in Alzheimer disease Mechanisms of ageing and development · 2016-04-20 · usefulness score 45/100 · Risk genes beyond APOE
• Antioxidants in Down syndrome Biochimica et biophysica acta · 2011-12-21 · usefulness score 39/100 · Down syndrome and Alzheimer's

Related studies in Risk genes beyond APOE

• Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression Antioxidants & redox signaling · 2013-02-14 · usefulness score 48/100
• In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid beta-peptide of APP Free radical biology & medicine · 2009-10-23 · usefulness score 47/100
• β-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease Free radical biology & medicine · 2010-10-26 · usefulness score 44/100
• Amyloid beta-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain Brain pathology (Zurich, Switzerland) · 2004-10-01 · usefulness score 41/100
• Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress The Journal of cell biology · 2002-03-18 · usefulness score 40/100
• Alzheimer´s disease and oxidative stress: a review Current medicinal chemistry · 2014-01-01 · usefulness score 39/100

Also in Risk genes beyond APOE

98 studies in the library are filed under Risk genes beyond APOE with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Risk genes beyond APOE hub.

• Cohort Profile Update: The ‘Seguimiento Universidad de Navarra’ (SUN) study after 24 years of follow-up International Journal of Epidemiology · 2025-08-01 · usefulness score 59/100 · Risk genes beyond APOE
• Too early for LATE? Age at onset is associated with the clinical and neuroimaging expression of limbic-predominant age- related TDP-43 pathology in Alzheimer’s disease medRxiv · 2026-10-20 · usefulness score 16/100 · Risk genes beyond APOE
• Sex-Based Differences in Perioperative Brain Health Outcomes A&A Practice · 2026-05-01 · usefulness score 57/100 · Risk genes beyond APOE

Similar studies

• Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease 2019 · Mild cognitive impairment
• Oxidative stress and the pathogenesis of neurodegenerative disorders 2007 · How common it is
• Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease 2010 · Brain tissue and pathology
• DOENÇA DE ALZHEIMER E SEUS MECANISMOS EPIGENÉTICOS 2025 · Genetics
• Alzheimer's disease treated patients showed different patterns for oxidative stress and inflammation markers 2013 · Disease mechanisms
• Oxidative Stress Hypothesis in Alzheimer's Disease 1997 · Disease mechanisms

More on Risk genes beyond APOE

• Newest in this subject Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Temporal Proteomics Links the APP London Mutation to Early Cholesterol Remodeling Cell Programs in Human Neurons bioRxiv · 2026-10-24 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Risk genes beyond APOE →