title: Immunohistochemical investigation of neurofibrillary tangles and their tau isoforms in brains of limbic neurofibrillary tangle dementia.
abstract: Limbic neurofibrillary tangle dementia (LNTD) is a subset of senile dementia characterized by numerous neurofibrillary tangles (NFT) in the hippocampal area, although there is an absence or scarcity of amyloid deposits (AM) throughout the brain. In the present study, we immunohistochemically investigated regional numbers and tau isoforms of NFT in the hippocampal area of nine LNTD patients with anti-three-repeat (3R) tau-specific and anti-four-repeat (4R) tau-specific antibodies, differentiating NFT into three developmental stages of pretangles (PT), NFT and ghost tangles (GT). Consequently, most PT were 4R tau-positive, most GT were 3R tau-positive, and NFT were 3R tau-, 4R tau- or double-positive, suggesting that composition of tau isoforms may shift from a 4R tau-predominant pattern to a 3R tau-predominant pattern during the development of NFT. In addition, a large number of NFT showing different developmental stages and different rates of 3R tau- and 4R tau-positive neurons according to the region were found in the hippocampal area, suggesting that regions undergoing earlier NFT formation may show higher ratio of 3R tau-positive neurons to 4R tau-positive neurons, and that NFT formation may begin in the entorhinal and transentorhinal cortices, subsequently progress to the subiculum and CA1, and further to the CA2, amygdala and CA3-4, although progression to the neocortex is limited. Furthermore, 4R tau-positive astrocytes and grains were found in several patients, suggesting that LNTD is a form of tauopathy.
authors.affiliation: Department of Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan. iseki@juntendo.gmc.ac.jp <iseki@juntendo.gmc.ac.jp>
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Murayama
authors.forename: Michiko
authors.initials: M
authors.lastname: Minegishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Togo
authors.forename: Omi
authors.initials: O
authors.lastname: Katsuse
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Lees
authors.initials: L
authors.lastname: Andrew
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000369:Aged, 80 and over; D003704:Dementia / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins