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Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study.

Publication ,  Journal Article
Kramer, PL; Xu, H; Woltjer, RL; Westaway, SK; Clark, D; Erten-Lyons, D; Kaye, JA; Welsh-Bohmer, KA; Troncoso, JC; Markesbery, WR; Petersen, RC ...
Published in: Neurobiol Aging
December 2011

Many elderly individuals remain dementia-free throughout their life. However, some of these individuals exhibit Alzheimer disease neuropathology on autopsy, evidenced by neurofibrillary tangles (NFTs) in AD-specific brain regions. We conducted a genome-wide association study to identify genetic mechanisms that distinguish non-demented elderly with a heavy NFT burden from those with a low NFT burden. The study included 299 non-demented subjects with autopsy (185 subjects with low and 114 with high NFT levels). Both a genotype test, using logistic regression, and an allele test provided consistent evidence that variants in the RELN gene are associated with neuropathology in the context of cognitive health. Immunohistochemical data for reelin expression in AD-related brain regions added support for these findings. Reelin signaling pathways modulate phosphorylation of tau, the major component of NFTs, either directly or through β-amyloid pathways that influence tau phosphorylation. Our findings suggest that up-regulation of reelin may be a compensatory response to tau-related or beta-amyloid stress associated with AD even prior to the onset of dementia.

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Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

December 2011

Volume

32

Issue

12

Start / End Page

2113 / 2122

Location

United States

Related Subject Headings

  • tau Proteins
  • Signal Transduction
  • Serine Endopeptidases
  • Reelin Protein
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Neurology & Neurosurgery
  • Neurofibrillary Tangles
  • Nerve Tissue Proteins
  • Male
 

Citation

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Kramer, P. L., Xu, H., Woltjer, R. L., Westaway, S. K., Clark, D., Erten-Lyons, D., … Ott, J. (2011). Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study. Neurobiol Aging, 32(12), 2113–2122. https://doi.org/10.1016/j.neurobiolaging.2010.01.010
Kramer, Patricia L., Haiyan Xu, Randall L. Woltjer, Shawn K. Westaway, David Clark, Deniz Erten-Lyons, Jeffrey A. Kaye, et al. “Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study.Neurobiol Aging 32, no. 12 (December 2011): 2113–22. https://doi.org/10.1016/j.neurobiolaging.2010.01.010.
Kramer PL, Xu H, Woltjer RL, Westaway SK, Clark D, Erten-Lyons D, et al. Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study. Neurobiol Aging. 2011 Dec;32(12):2113–22.
Kramer, Patricia L., et al. “Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study.Neurobiol Aging, vol. 32, no. 12, Dec. 2011, pp. 2113–22. Pubmed, doi:10.1016/j.neurobiolaging.2010.01.010.
Kramer PL, Xu H, Woltjer RL, Westaway SK, Clark D, Erten-Lyons D, Kaye JA, Welsh-Bohmer KA, Troncoso JC, Markesbery WR, Petersen RC, Turner RS, Kukull WA, Bennett DA, Galasko D, Morris JC, Ott J. Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study. Neurobiol Aging. 2011 Dec;32(12):2113–2122.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

December 2011

Volume

32

Issue

12

Start / End Page

2113 / 2122

Location

United States

Related Subject Headings

  • tau Proteins
  • Signal Transduction
  • Serine Endopeptidases
  • Reelin Protein
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Neurology & Neurosurgery
  • Neurofibrillary Tangles
  • Nerve Tissue Proteins
  • Male