title: Accumulation of carboxy-terminal fragments of APP increases phosphodiesterase 8B.
abstract: The long-standing "amyloid hypothesis" that Alzheimer's disease is caused by the production and aggregation of amyloid-β faces serious challenges by data recently obtained from neuroimaging studies and amyloid-β amyloid-focused clinical trials. Meanwhile, accumulation of carboxy-terminal fragments (CTFs) of the amyloid precursor protein (APP) may be neurotoxic and may impair synaptic plasticity and long-term memory in Alzheimer's disease, as suggested in murine models. To clarify these issues, we carried out a proteomic analysis of Chinese hamster ovary cells expressing APP CTFs and found that APP-CTF accumulation induced an increase in the level of phosphodiesterase 8B, suggesting that the hydrolysis of cyclic AMP was enhanced.
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address: kametani-fy@igakuken.or.jp.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Haga
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008568:Memory; D051379:Mice; D059906:Neuroimaging / Q000379:methods; D009473:Neuronal Plasticity; D040901:Proteomics
chemical_list: D016564:Amyloid beta-Protein Precursor; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human
keywords: APP; Alzheimer's disease; Amyloid; Aβ; CTF; Phosphodiesterase; Proteomics; cAMP