title: Characterization and distribution of adaptor protein containing a PH domain, PTB domain and leucine zipper motif (APPL1) in Alzheimer's disease hippocampus: an immunohistochemical study.
abstract: Adaptor protein containing a PH domain, PTB domain and leucine zipper motif (APPL1) is emerging as a critical regulator of various cellular processes in non-neuronal cells as well as in neurons where it localizes to dendritic spines and synapses. It regulates the development of these structures in hippocampal neurons. Although memory impairment in Alzheimer's disease (AD) has been attributed to disruption of synaptic plasticity, there is scant information on this protein in the human brain. In the present study, we immunohistochemically characterized the localization of APPL1 in AD and control brains. APPL1 accumulated perisomatically as granules around neurons within vulnerable sectors of the hippocampus (CA1 and subiculum) in AD brain, whilst APPL1-positive granules were rarely identified in control brains derived from elderly individuals with no known cognitive impairment. Interestingly, in the AD hippocampus, APPL1 also co-localized with perisomatic granules (non-plaque dystrophic dendrites) expressing glutamate receptor 2 and ubiquitin, suggesting the possible involvement of APPL1 in the synaptic modifications in AD. Thus, the immunohistochemical distribution of APPL1 in AD brain was distinct from that in non-AD control brains, suggesting that signaling via APPL1 might play a critical role in the memory impairment in AD.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Ogawa
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurashige
authors.forename: Masanori
authors.initials: M
authors.lastname: Hiji
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nagano
authors.forename: Takemori
authors.initials: T
authors.lastname: Yamawaki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016022:Case-Control Studies; D005110:Extracellular Space; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018091:Receptors, AMPA / Q000378:metabolism; D012016:Reference Values; D014018:Tissue Distribution; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018091:Receptors, AMPA; D025801:Ubiquitin