Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy. Issue 10 (25th August 2022)

• Record Type: Journal Article
• Authors: Farrell, Kurt; Iida, Megan A; Cherry, Jonathan D; Casella, Alicia; Stein, Thor D; Bieniek, Kevin F; Walker, Jamie M; Richardson, Timothy E; White, Charles L; Alvarez, Victor E; Huber, Bertrand R; Dickson, Dennis W; Insausti, Ricardo; Dams-O'Connor, Kristen; McKee, Ann C; Crary, John F
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 81:Issue 10(2022)
• Page Start: 781
• Page End: 789
• Publication Date: 2022-08-25
• Subjects: Aging -- Chronic traumatic encephalopathy -- Primary age-related tauopathy -- Repetitive head impacts -- Tauopathy; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac066
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: 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 = 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p = 0.02) and CA4 (p = 0.01) and total p-tau burden in CA2 trended higher than CA4 (p = 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 = 0.01, p = 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.