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

Lookup NU author(s): Professor Johannes Attems


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

Publication metadata

Author(s): Walker JM, Richardson TE, Farrell K, Iida MA, Foong C, Shang P, Attems J, Ayalon G, Beach TG, Bigio EH, Budson A, Cairns NJ, Corrada M, Cortes E, Dickson DW, Fischer P, Flanagan ME, Franklin E, Gearing M, Glass J, Hansen LA, Haroutunian V, Hof PR, Honig L, Kawas C, Keene CD, Kofler J, Kovacs GG, Lee EB, Lutz MI, Mao Q, Masliah E, McKee AC, McMillan CT, Mesulam MM, Murray M, Nelson PT, Perrin R, Pham T, Poon W, Purohit DP, Rissman RA, Sakai K, Sano M, Schneider JA, Stein TD, Teich AF, Trojanowski JQ, Troncoso JC, Vonsattel J-P, Weintraub S, Wolk DA, Woltjer RL, Yamada M, Yu L, White CL, Crary JF

Publication type: Article

Publication status: Published

Journal: Journal of Neuropathology and Experimental Neurology

Year: 2021

Volume: 80

Issue: 2

Pages: 102-111

Print publication date: 01/02/2021

Online publication date: 17/01/2021

Acceptance date: 02/04/2018

ISSN (print): 0022-3069

ISSN (electronic): 1554-6578

Publisher: Oxford University Press


DOI: 10.1093/jnen/nlaa153

PubMed id: 33367843


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