[Etiology and pathogenesis of Alzheimer dementia].
Alzheimer's disease (AD) is the most common cause of primary dementia, characterized by a progressive process of pathophysiological restructuring of the brain over decades. The hallmark of Alzheimer's disease is the extracellular accumulation and deposition of insoluble amyloid, to be found in the parenchyma in the form of amyloid plaques and in meningeal and cerebral vessels as a congophile angiopathy. Equally conspicuous is the intraneuronal occurrence of neurofibrillary tangles, consisting mainly of hyperphosphorylated tau-protein. Amyloid plaques and neurofibrillary tangles are characteristic, but not specific to Alzheimer's disease. Similar changes can be found in healthy ageing processes and in various other neurodegenerative diseases. It is common to differentiate between an early-onset, familial Alzheimer's disease with an established genetic etiology, representing only about 5% of all cases, and the more typical late-onset, sporadic Alzheimer's disease with an age of onset above 65 years and no clear pattern of inheritance. Although there seems to be a large heterogeneity in the etiology of Alzheimer's disease, the amyloid-cascade-hypothesis has taken a central position as a model for the general etiopathogenesis. The regulation of amyloid plaques underlies a diversity of cellular and molecular factors. In addition to ageing, apolipoprotein E 4 is a firmly established risk factor. Disturbance in the cerebral glucose metabolism, especially in the hippocampal regions, is a further proposed factor in the pathogenesis of Alzheimer's disease. The wide-spread loss of cortical cholinergic neurotransmission associated with the cognitive deficits is of importance to the comprehension of the symptoms and the present pharmacotherapy of Alzheimer's disease.
Kratzsch
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Klinik für Psychiatrie und Psychotherapie I, Universitätsklinik der Johann-Wolfgang-Goethe-Universität Frankfurt am Main, Heinrich-Hoffmann-Strasse 10, D-60528 Frankfurt am Main, Deutschland. Kratzsch@em.uni-frankfurt.de
Peters
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J
Frölich
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D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology; D001921:Brain / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology
D007328:Insulin; D018377:Neurotransmitter Agents
Atiologie und Pathogenese der Alzheimer-Demenz.