Skip to main content
Top
Published in: Acta Neuropathologica Communications 1/2021

Open Access 01-12-2021 | Alzheimer's Disease | Research

Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

Authors: Jonathan D. Cherry, Camille D. Esnault, Zachary H. Baucom, Yorghos Tripodis, Bertrand R. Huber, Victor E. Alvarez, Thor D. Stein, Dennis W. Dickson, Ann C. McKee

Published in: Acta Neuropathologica Communications | Issue 1/2021

Login to get access

Abstract

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.
Literature
2.
7.
go back to reference Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 82:239–259CrossRefPubMed Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 82:239–259CrossRefPubMed
12.
26.
go back to reference Love S, Louis D, Ellison DW (2008) Greenfield’s neuropathology, vol 2, 8th edn. CRC Press, Boca Raton, FLCrossRef Love S, Louis D, Ellison DW (2008) Greenfield’s neuropathology, vol 2, 8th edn. CRC Press, Boca Raton, FLCrossRef
31.
go back to reference McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 9:417–423CrossRefPubMed McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 9:417–423CrossRefPubMed
Metadata
Title
Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease
Authors
Jonathan D. Cherry
Camille D. Esnault
Zachary H. Baucom
Yorghos Tripodis
Bertrand R. Huber
Victor E. Alvarez
Thor D. Stein
Dennis W. Dickson
Ann C. McKee
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2021
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-021-01189-4

Other articles of this Issue 1/2021

Acta Neuropathologica Communications 1/2021 Go to the issue