[The pathogenesis of Alzheimer's disease demonstrated by immunocytochemistry with anti-beta-protein antibody].
Alzheimer's disease is the most common cause of dementia in the elderly. The characteristic neuropathologic findings in this disease are neurofibrillary tangles, senile plaques, and often amyloid infiltration of cerebrovascular walls. These lesions are commonly found in the neocortex and hippocampus, and their clinical significance has been highlighted by quantitative studies showing a significant correlation between the numbers of neurofibrillary tangles and senile plaques and the clinical severity of dementia. In 1984, Glenner and Wong isolated a novel protein (termed "beta-protein") from cerebrovascular amyloid of individuals with Alzheimer's disease and adult Down's syndrome. In the following year, Masters et al, using amino acid sequence data, demonstrated that beta-protein is also a component of senile plaque amyloid fibrils. Subsequently, this chemical data was supported by light microscopic and electron microscopic immunohistochemical studies showing that cerebrovascular and senile plaque amyloid deposits are reactive to synthetic beta-protein peptide antibodies. In addition, some recent histochemical and immunocytochemical studies have revealed important new information on the pathogenesis of the senile plaque: senile plaques may undergo sequential structural changes. On the basis of the investigation on a series of Down's syndrome cases, an extensive appearance of beta-protein deposits is an early pathologic change in Alzheimer's disease, and the formation of neurofibrillary changes, including tangles, develops at an advanced stage. The availability of beta-protein amino acid sequence data led to the identification of a full-length cDNA clone coding a possible precursor of amyloid beta-protein. However, the origin or function of this beta-protein precursor still remains uncertain. Further studies are required to know the exact pathogenesis of Alzheimer's disease.
Ikeda
S
S
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan.
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data
D016229:Amyloid beta-Peptides