001     272672
005     20241020000055.0
024 7 _ |a 10.3233/JAD-240483
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024 7 _ |a 1387-2877
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024 7 _ |a 1875-8908
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037 _ _ |a DZNE-2024-01223
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Del Tredici, Kelly
|b 0
245 _ _ |a Early CA2 Tau Inclusions Do Not Distinguish an Age-Related Tauopathy from Early Alzheimer's Disease.
260 _ _ |a Amsterdam
|c 2024
|b IOS Press
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520 _ _ |a 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.
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650 _ 7 |a APOE
|2 Other
650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a Ammon’s horn
|2 Other
650 _ 7 |a CA2
|2 Other
650 _ 7 |a PART hypothesis
|2 Other
650 _ 7 |a entorhinal cortex
|2 Other
650 _ 7 |a neurofibrillary tangles
|2 Other
650 _ 7 |a pretangles
|2 Other
650 _ 7 |a tau seeding
|2 Other
650 _ 7 |a tractus perforans
|2 Other
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Tauopathies: pathology
|2 MeSH
650 _ 2 |a Tauopathies: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Entorhinal Cortex: pathology
|2 MeSH
650 _ 2 |a Entorhinal Cortex: metabolism
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a CA2 Region, Hippocampal: pathology
|2 MeSH
650 _ 2 |a CA2 Region, Hippocampal: metabolism
|2 MeSH
650 _ 2 |a Inclusion Bodies: pathology
|2 MeSH
650 _ 2 |a Inclusion Bodies: metabolism
|2 MeSH
650 _ 2 |a Neurofibrillary Tangles: pathology
|2 MeSH
650 _ 2 |a Neurofibrillary Tangles: metabolism
|2 MeSH
650 _ 2 |a Aging: pathology
|2 MeSH
650 _ 2 |a Aging: metabolism
|2 MeSH
700 1 _ |a Schön, Michael
|b 1
700 1 _ |a Feldengut, Simone
|b 2
700 1 _ |a Ghebremedhin, Estifanos
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700 1 _ |a Kaufman, Sarah K
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700 1 _ |a Wiesner, Diana
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700 1 _ |a Roselli, Francesco
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700 1 _ |a Mayer, Benjamin
|b 7
700 1 _ |a Amunts, Katrin
|b 8
700 1 _ |a Braak, Heiko
|b 9
773 _ _ |a 10.3233/JAD-240483
|g Vol. 101, no. 4, p. 1333 - 1353
|0 PERI:(DE-600)2070772-1
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|p 1333 - 1353
|t Journal of Alzheimer's disease
|v 101
|y 2024
|x 1387-2877
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