[Biological characteristics of amyloid precursor protein and Alzheimer's disease].
Recent advances in Alzheimer's disease (AD) research were briefly reviewed. AD is the most common cause of progressive intellectual decline in the aged in the Western world and also in Japan. The AD-affected brain is characterized by numerous amyloid plaques, neurofibrillary tangles, and neuronal losses. The amyloid deposition is considered to be more important because it appears first, and is followed by NFTs. The amyloid is composed of amyloid beta peptide (Abeta), a 40 approximately 42 amino acid fragment of the large membrane protein, amyloid precursor protein (APP). Abeta is cleaved by the proteolytic enzymes, beta, and gamma secretase. Considerable effort has been directed to identify these enzymes, and to find the intracellular compartments where Abeta is generated. The lysosome, or related acidic compartment is one of the candidates. The N and C terminis of the Abeta is known to vary slightly. Biochemical and immunopathological studies implicate that Abeta42 is more important than Abeta40 in the pathogenesis of AD. On the other hand, many missense mutations in APP gene and other genes, e.g. S182, and STM 2 have been identified in familial AD. Neuropathologically, AD is regarded as cerebral Abeta amyloidosis. The AD amyloid is composed of many proteins other than Abeta, designated as amyloid associated proteins. These proteins may play important roles in amyloid formation, since Abeta itself is soluble. Transgenic mice and chloroquine myopathy rat are available as animal models for AD. Elucidation of the roles of these missense mutations, and amyloid associated proteins in the cascade of AD, may provide a breakthrough to therapeutics for AD.
Fukatsu
R
R
Department of Neuropsychiatry, Sapporo Medical University, School of Medicine, Japan.
Tsuzuki
K
K
Takamaru
Y
Y
Hayashi
Y
Y
Sasaki
N
N
Yoshida
T
T
Midorikawa
Y
Y
Fujii
N
N
Takahata
N
N
D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002875:Chromosomes; D004195:Disease Models, Animal; D006801:Humans; D009154:Mutation
D016564:Amyloid beta-Protein Precursor