Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy

Kurt Farrell, Megan A. Iida, Jonathan D. Cherry, Alicia Casella, Thor D. Stein, Kevin F. Bieniek, Jamie M. Walker, Timothy E. Richardson, Charles L. White, Victor E. Alvarez, Bertrand R. Huber, Dennis W. Dickson, Ricardo Insausti, Kristen Dams-O’Connor, Ann C. McKee, John F. Crary

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortical sulci. In moderate to advanced CTE, NFTs accumulate in the hippocampus, potentially overlapping neuroanatomically with primary age-related tauopathy (PART), an age-related tauopathy characterized by Alzheimer disease-like tau pathology in the hippocampus devoid of amyloid plaques. We measured p-tau burden using positive-pixel counts on immunohistochemically stained and neuroanatomically segmented hippocampal tissue. Subjects with CTE had a higher total p-tau burden than PART subjects in all sectors (p ¼ 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p ¼ 0.02) and CA4 (p ¼ 0.01) and total p-tau burden in CA2 trended higher than CA4 (p ¼ 0.06). In CTE, total p-tau burden in CA1/subiculum was significantly higher than in the dentate gyrus; and CA2 also trended higher than dentate gyrus (p ¼ 0.01, p ¼ 0.06). When controlling for p-tau burden across the entire hippocampus, CA3 and CA4 had significantly higher p-tau burden in CTE than PART (p < 0.0001). These data demonstrate differences in hippocampal p-tau burden and regional distribution in CTE compared to PART that might be helpful in differential diagnosis and reveal insights into disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number10
StatePublished - Oct 1 2022


  • Aging
  • Chronic traumatic encephalopathy
  • Primary age-related tauopathy
  • Repetitive head impacts
  • Tauopathy

ASJC Scopus subject areas

  • General Medicine


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