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F4‐01‐01: DISTRIBUTION AND CHARACTERISTICS OF TAU AGGREGATES ACROSS ALZHEIMER DISEASE STAGES
Author(s) -
Duyckaerts Charles
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.04.362
Subject(s) - senile plaques , neocortex , entorhinal cortex , tauopathy , neurofibrillary tangle , neuropil , neuroscience , dentate gyrus , pathology , hippocampus , locus coeruleus , alzheimer's disease , biology , neurodegeneration , medicine , disease , central nervous system
Background: Neurofibrillary tangles, one of the hallmark lesions of Alzheimer disease (AD), are made of aggregated hyperphosphorylated tau (hpTau). Accumulation of hpTau in dendrites constitute neuropil threads. Some of the axonal processes of the senile plaque corona also contain hpTau. Neurofibrillary tangles, neuropil threads and neuritic plaques progress in a stepwise manner.Methods: The stereotyped distribution of the lesions is well described by Braak stages. Some specific monoclonal antibodies, such as AT8, immunostain the tauopathy with high sensitivity and specificity. Results: The affected neurons and their processes are initially fully immunostained. The dendrites are secondarily isolated from the cell body and constitute the neuropil threads. The relation between the tangle-bearing neurons and the tau positive axons of the senile plaque corona remains poorly understood. Early tangles and threads are located in the trans-entorhinal and entorhinal areas. The senile plaques then appear in the molecular layer of the dentate gyrus; their corona is made of axons from layer II entorhinal neurons. After involvement of the hippocampus, the neocortex is affected: in the neocortex, tau-free amyloid deposits are first visible before tau positive threads become apparent. The amyloid cores are but secondarily surrounded by tau positive axons. Tangles are last. Recent data by Braak & Del Tredici as well as by other groups indicate that brainstem involvement (particularly of the locus coeruleus) could precede the entorhinal stages. Conclusions: The progression follows anatomical pathways. Recent experiments of injections of tau homogenates in transgenic or wild type mice suggest a prionlike mode of propagation of the tauopathy.