[Alzheimer's dementia and amyloid precursor-protein].
Alzheimer's dementia is a severe form of dementia characterised by three neuropathological changes: amyloid plaques, neurofibrillary tangles and neurodegeneration. Several laboratories are involved in studies of the molecular mechanisms underlying development of Alzheimer's disease. As a result of recent research, the main component of amyloid plaques, the beta A4-peptide, is focused upon in hypotheses of the pathogenesis of the disease. The beta A4-peptide is produced by cleavage of the larger amyloid precursor protein (APP). During normal processing of APP, production of beta A4 is hindered and the peptide is therefore presumably a result of alternative cleavage mechanisms. Several factors may increase alternative processing of APP. One possibility is that conformational changes in APP, e.g. induced by mutations in the APP gene, may facilitate alternative cleavage of APP and thereby production of beta A4. This seems to be the case in certain families with familial Alzheimer's disease. Another possibility for increased beta A4 production is excessive expression of APP. This seems to be the case in persons with trisomy 21 who all have neuropathological signs of Alzheimer's disease after the age of 40 years. The gene for APP is localised to the human chromosome 21 and these persons have 1.5 times the normal expression of APP. Furthermore, excessive APP-expression may be induced by an acute phase response in the brain. In vitro studies and neuropathological examinations indicate that alpha 2-macroglobulin in neurons may be induced by cytokines. The protease inhibitor activity of this protein may prevent normal cleavage of APP, thereby resulting in increased alternative cleavage and deposition of beta A4.(ABSTRACT TRUNCATED AT 250 WORDS)
Blom
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Proteinlaboratoriet, Københavns Universitet.
Linnemann
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D
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics*; D006801:Humans
D016564:Amyloid beta-Protein Precursor
Alzheimer's demens og amyloid precursor-protein.