Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy

Jamie M. Walker, Timothy E. Richardson, Kurt Farrell, Megan A. Iida, Chan Foong, Ping Shang, Johannes Attems, Gai Ayalon, Thomas G. Beach, Eileen H. Bigio, Andrew Budson, Nigel J. Cairns, María Corrada, Etty Cortes, Dennis W. Dickson, Peter Fischer, Margaret E. Flanagan, Erin Franklin, Marla Gearing, Jonathan GlassLawrence A. Hansen, Vahram Haroutunian, Patrick R. Hof, Lawrence Honig, Claudia Kawas, C. Dirk Keene, Julia Kofler, Gabor G. Kovacs, Edward B. Lee, Mirjam I. Lutz, Qinwen Mao, Eliezer Masliah, Ann C. McKee, Corey T. McMillan, M. Marsel Mesulam, Melissa Murray, Peter T. Nelson, Richard Perrin, Thao Pham, Wayne Poon, Dushyant P. Purohit, Robert A. Rissman, Kenji Sakai, Mary Sano, Julie A. Schneider, Thor D. Stein, Andrew F. Teich, John Q. Trojanowski, Juan C. Troncoso, Jean Paul Vonsattel, Sandra Weintraub, David A. Wolk, Randall L. Woltjer, Masahito Yamada, Lei Yu, Charles L. White, John F. Crary

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish
Pages (from-to)102-111
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number2
StatePublished - Feb 1 2021

Bibliographical note

Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.


  • Alzheimer disease
  • CA2
  • Cognitive status
  • Cornu ammonis
  • Hippocampal subfields
  • Neurodegenerative disease
  • Primary age-related tauopathy

ASJC Scopus subject areas

  • General Medicine


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