Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies

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Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies

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Title: Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies
Author: Chibnik, Lori B; White, Charles C; Mukherjee, Shubhabrata; Raj, Towfique; Yu, Lei; Larson, Eric B.; Montine, Thomas J.; Keene, C. Dirk; Sonnen, Joshua; Schneider, Julie A.; Crane, Paul K.; Shulman, Joshua M.; Bennett, David A; De Jager, Philip L

Note: Order does not necessarily reflect citation order of authors.

Citation: Chibnik, L. B., C. C. White, S. Mukherjee, T. Raj, L. Yu, E. B. Larson, T. J. Montine, et al. 2017. “Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.” Molecular psychiatry :10.1038/mp.2017.20. doi:10.1038/mp.2017.20. http://dx.doi.org/10.1038/mp.2017.20.
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Abstract: Tauopathies, including Alzheimer’s disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFT). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, p=3.8×10−8) in 909 prospective autopsies. The association is replicated in an independent dataset of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we find that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid β plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies which co-exist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid β plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common endpoint for multiple different pathologic processes.
Published Version: doi:10.1038/mp.2017.20
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608624/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492045
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