Journal Article

DZNE-2024-01223

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Early CA2 Tau Inclusions Do Not Distinguish an Age-Related Tauopathy from Early Alzheimer's Disease.

Del Tredici, K. ; Schön, M. ; Feldengut, S. ; Ghebremedhin, E. ; Kaufman, S. K. ; Wiesner, D.DZNE* ; Roselli, F.DZNE* ; Mayer, B. ; Amunts, K. ; Braak, H.

2024
IOS Press Amsterdam

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Please use a persistent id in citations: doi:10.3233/JAD-240483

Abstract: Neuropathologic studies of brains from autopsy series show tau inclusions (pretangles, neuropils threads, neurofibrillary tangles) are detectable more than a decade before amyloid-β (Aβ) deposition in Alzheimer's disease (AD) and develop in a characteristic manner that forms the basis for AD staging. An alternative position views pathological tau without Aβ deposition as a 'primary age-related tauopathy' (PART) rather than prodromal AD. Recently, an early focus of tau inclusions in the Ammon's horn second sector (CA2) with relative sparing of CA1 that occurs before tau inclusions develop in the entorhinal cortex (EC) was proposed as an additional feature of PART.To test the 'definite PART' hypothesis.We used AT8-immunohistochemistry in 100μm sections to examine the EC, transentorhinal cortex (TRE), and Ammon's horn in 325 brains with tau inclusions lacking Aβ deposits (average age at death 66.7 years for females, 66.4 years for males).100% of cases displayed tau inclusions in the TRE. In 89% of cases, the CA1 tau rating was greater than or equal to that in CA2. In 25%, CA2 was devoid of tau inclusions. Only 4% displayed a higher tau score in CA2 than in the TRE, EC, and CA1. The perforant path also displayed early tau changes. APOE genotyping was available for 199/325 individuals. Of these, 44% had an ɛ4 allele that placed them at greater risk for developing later NFT stages and, therefore, clinical AD.Our new findings call into question the PART hypothesis and are consistent with the idea that our cases represent prodromal AD.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Tauopathies: pathology (MeSH) ; Tauopathies: metabolism (MeSH) ; tau Proteins: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; Entorhinal Cortex: pathology (MeSH) ; Entorhinal Cortex: metabolism (MeSH) ; Middle Aged (MeSH) ; CA2 Region, Hippocampal: pathology (MeSH) ; CA2 Region, Hippocampal: metabolism (MeSH) ; Inclusion Bodies: pathology (MeSH) ; Inclusion Bodies: metabolism (MeSH) ; Neurofibrillary Tangles: pathology (MeSH) ; Neurofibrillary Tangles: metabolism (MeSH) ; Aging: pathology (MeSH) ; Aging: metabolism (MeSH) ; APOE ; Alzheimer’s disease ; Ammon’s horn ; CA2 ; PART hypothesis ; entorhinal cortex ; neurofibrillary tangles ; pretangles ; tau seeding ; tractus perforans ; tau Proteins

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Contributing Institute(s):

1. Metabolic Changes in Neurodegeneration (AG Roselli)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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