title: Immunohistochemical study of tau accumulation in early stages of Alzheimer-type neurofibrillary lesions.
abstract: Accumulation of abnormally phosphorylated tau results in the formation of neurofibrillary tangles (NFTs) in the neuronal cell soma and neuropil threads (NTs) in the cell processes. In the present study, we used immunohistochemistry to investigate serially cut thick tissue sections from the brains of patients with Alzheimer's disease (AD) and non-demented elderly subjects. In the early stages of neurofibrillary pathology, clusters of NTs occurred occasionally in the cerebral cortex. Each NTs cluster, the entire extent of which was observed in the serial sections, corresponded to a dendritic tree that was arborized from a tau-positive neuron. Adult human brain contains six tau isoforms with three having three carboxyl-terminal tandem repeat sequences that are encoded by exon 10 (3R-tau) and the other three having four repeat sequences (4R-tau). Three isoform patterns, 3R-tau(+)/4R-tau(-), 3R-tau(-)/4R-tau(+) and 3R-tau(+)/4R-tau(+), were seen in NFTs in early stage AD lesions. In an individual neuron, the isoform pattern was consistent between the NFTs in the cell soma and the NTs in the cell processes. The results of this study indicate that, in early stages of AD and age-associated neurofibrillary changes, tau accumulates simultaneously in the cell soma and cell processes of affected neurons. The process of AD and age-associated tau pathology is not tau-isoform-specific, but the ratio of 3R-tau and 4R-tau isoforms involved in the neurofibrillary changes varies and is specific to individual neurons.
authors.affiliation: Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585 Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Togo
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Hirotake
authors.initials: H
authors.lastname: Uchikado
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kondo
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins