CoChat
Sign Up
Cited by 162Epigenetics and DNA MethylationHeavy Metal Exposure and ToxicityAlzheimer's disease research and treatments

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: implications for Alzheimer’s disease

Bihaqi, Syed Waseem, Huang, Hui, Wu, Jinfang, Zawia, Nasser H.·2011·Journal of Alzheimer’s Disease
DOI 10.3233/jad-2011-111013
Open this paper in CoChat — free account

Abstract

The beginnings of late onset Alzheimer's disease (LOAD) are still unknown; however, the progressive and latent nature of neurodegeneration suggests that the triggering event occurs earlier in life. Aging primates exposed to lead (Pb) as infants exhibited an overexpression of the amyloid-β protein precursor (AβPP), amyloid-β (Aβ) and enhanced pathologic neurodegeneration. In this study, we measured the latent expression of a wide array of brain-specific genes and explored whether epigenetic pathways mediated such latent molecular and pathological changes. We analyzed the levels of proteins associated with DNA methylation, i.e., DNA methyltransferase 1 (Dnmt1), DNA methyltransferase3a (Dnmt3a), methyl-CpG binding protein-2 (MeCP2) and those involved in histone modifications (acetylated and methylated histones). We monitored the expression profiles of these intermediates across the lifespan and analyzed their levels in 23-year-old primate brains exposed to Pb as infants. Developmental Pb exposure altered the gene expression of the arrayed genes, which were predominately repressed, with fewer upregulated genes. The latent induction and repression of genes was accompanied by a significant decrease in the protein levels of Dnmts, MeCP2, and proteins involved in histone modifications. The attenuation of DNA methylation enzymes is consistent with hypomethylating effects, which promote upregulation of the genes, while the alterations in the histone modifiers are associated with the repression of genes. Hence, we deduce that early life exposure to Pb can reprogram gene expression resulting in both upregulation and down-regulation of genes through alternate epigenetic pathways contributing to an enhancement in neurodegeneration in old age.

Overview

Integrity signals

Registry

Crossref · 10.3233/jad-2011-111013

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

Sorted by citations

See all 162

Related

See all

Metadata

Authors
Bihaqi, S. W., Huang, H., Wu, J., & Zawia, N. H.
Affiliations
  • University of Rhode Island (US)
  • Zhengzhou University (CN)
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2011-12-12
Volume
27
Issue
4
Pages
819-833
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-2011-111013
OpenAlex
W1693568153
Cited by
162
References
60
Citations by year
2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 14 · 2019: 14 · 2018: 10 · 2017: 12 · 2016: 15 · 2015: 12 · 2014: 19 · 2013: 14 · 2012: 10
FWCI
5.72
Type
journal article
Language
en
Open access
closed
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute for Health and Care Research
  • Institute of Environmental Science and Research
  • National Institute of Environmental Research
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (R01ES015867)
  • National Center for Research Resources (P20RR016457)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
lead exposure
MeSH terms
Age Factors, Aging, Animals, Animals, Newborn, Disease Models, Animal, Female, Humans, Lead, Lead Poisoning, Macaca fascicularis, Nerve Tissue Proteins, RNA, Messenger, Transcription Factors, DNA Modification Methylases, Cohort Studies, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, DNA Methylation, rab5 GTP-Binding Proteins, Epigenesis, Genetic, Methyl-CpG-Binding Protein 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review