@article{835f0403685d4d2ea5db551fab1de8fc,
title = "Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy",
abstract = "Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914). We found an early vulnerability of the CA2 subregion of the hippocampus to neurofibrillary degeneration in PART, and semiquantitative assessment of neurofibrillary degeneration in CA2 was significantly greater than in CA1 in PART. In contrast, subjects harboring intermediate-to-high AD neuropathologic change (ADNC) displayed relative sparing of CA2 until later stages of their disease course. In addition, the CA2/CA1 ratio of neurofibrillary degeneration in PART was significantly higher than in subjects with intermediate-to-high ADNC burden. Furthermore, the distribution of tau pathology in PART diverges from the Braak NFT staging system and Braak stage does not correlate with cognitive function in PART as it does in individuals with intermediate-to-high ADNC. These findings highlight the need for a better understanding of the contribution of PART to cognitive impairment and how neurofibrillary degeneration interacts with Aβ pathology in AD and PART.",
keywords = "Alzheimer disease, CA2, Cognitive status, Cornu ammonis, Hippocampal subfields, Neurodegenerative disease, Primary age-related tauopathy",
author = "Walker, {Jamie M.} and Richardson, {Timothy E.} and Kurt Farrell and Iida, {Megan A.} and Chan Foong and Ping Shang and Johannes Attems and Gai Ayalon and Beach, {Thomas G.} and Bigio, {Eileen H.} and Andrew Budson and Cairns, {Nigel J.} and Mar{\'i}a Corrada and Etty Cortes and Dickson, {Dennis W.} and Peter Fischer and Flanagan, {Margaret E.} and Erin Franklin and Marla Gearing and Jonathan Glass and Hansen, {Lawrence A.} and Vahram Haroutunian and Hof, {Patrick R.} and Lawrence Honig and Claudia Kawas and Keene, {C. Dirk} and Julia Kofler and Kovacs, {Gabor G.} and Lee, {Edward B.} and Lutz, {Mirjam I.} and Qinwen Mao and Eliezer Masliah and McKee, {Ann C.} and McMillan, {Corey T.} and Mesulam, {M. Marsel} and Melissa Murray and Nelson, {Peter T.} and Richard Perrin and Thao Pham and Wayne Poon and Purohit, {Dushyant P.} and Rissman, {Robert A.} and Kenji Sakai and Mary Sano and Schneider, {Julie A.} and Stein, {Thor D.} and Teich, {Andrew F.} and Trojanowski, {John Q.} and Troncoso, {Juan C.} and Vonsattel, {Jean Paul} and Sandra Weintraub and Wolk, {David A.} and Woltjer, {Randall L.} and Masahito Yamada and Lei Yu and White, {Charles L.} and Crary, {John F.}",
note = "Funding Information: Funding for this work was provided by International Institutional NIH/NIA Alzheimer Disease Center grants and private grants, including: R01 NS095252, R01 AG054008, R01 AG062348, F32 AG056098, P30 AG010161, P50 AG005136, U01 AG006781, P30 AG010124, P30 AG062429, P01 AG017586, R56 AG058732, P30 AG028383, P50 AG005131, P50 AG005133, P50 AG005138, P30 AG066514, P50 AG005681, P01 AG003991, P01 AG026276, U24 NS072026, P30 AG019610, P30 AG013854, P30 NS055077, P50 AG025688, R01 AG021055, P50 AG016573, P50 AG008702, P30 AG08017, the Alzheimer's Association (NIRG-15-363188), the Rainwater Charitable Foundation (Tau Consortium), David and Elsie Werber, J.M.R. Barker Foundation, The McCune Foundation, and the Winspear Family Center for Research on the Neuropathology of Alzheimer Disease, Knight Alzheimer Disease Research Center, The Arizona Department of Health Services, and the Michael J. Fox Foundation for Parkinson's Research. The authors would like to thank Allison Beller and Kim Howard at University of Washington, Jeff Harris at UTSW, The Betty Martz Laboratory for Neurodegenerative Research, UCSD Alzheimer Disease Research Center personnel, The Neuropathology Core of the Massachusetts Alzheimer Disease Research Center, Ryan Cassidy Bohannan and Chad Caraway at the UCI Brain Repository, and the Neuropathology Brain Bank & Research CoRE at Mount Sinai. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council (G0400074), by Brains for Dementia research, a joint venture between Alzheimer's Society and Alzheimer's Research UK, and by the NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. We acknowledge support from the Nancy and Buster Alvord Endowment, the J.M.R. Barker Foundation, the University of Texas Science and Technology Acquisition and Retention program award, and the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at the Joe and Teresa Long School of Medicine, University of Texas Health Sciences Center, San Antonio, TX. In addition, the authors would also like to thank all of the brain donors for allowing this work to be possible. Publisher Copyright: {\textcopyright} 2020 American Association of Neuropathologists, Inc. All rights reserved.",
year = "2021",
month = feb,
day = "1",
doi = "10.1093/jnen/nlaa153",
language = "English (US)",
volume = "80",
pages = "102--111",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
publisher = "Oxford University Press",
number = "2",
}