Unravelling the Molecular Defect in Alzheimer’s Disease
Dementia is of growing concern and social impact in the countries of the industrialized world where a strong rise in life expectancy has now led to increased interest in the biology of aging and in the pathology of age-associated diseases. Among these, Alzheimer’s disease (AD) is the most frequent cause of dementia and as such already the fourth leading cause of death. Its pathological basis was defined by Alois Alzheimer in 1907 in a case report on a presenile demented patient in whom intracerebral deposits with histochemical properties typical for amyloid were the main histological finding . These deposits are, as is characteristic for amyloid, congo red positive and green-red birefringent with polarized light and are found within neurons as neurofibrillary tangles, between neurons and glial cells as senile plaques, and within the walls of small cerebral and leptomeningeal blood vessels as vascular amyloid of congophilic angiopathy. The cerebral amyloid protein of AD is highly insoluble, and only in recent years have suitable purification techniques been developed. In 1984, Glenner and Wong  described the sequence of a major component of cerebrovascular amyloid, and in 1985 our laboratories analyzed the amyloid protein from senile plaques of AD and individuals with Down’s syndrome (DS) . In both instances, an almost identical polypeptide of 42/43 residues was found which is now termed βA4 protein according to its β-pleated sheet structure and its molecular weight of 4.5 kDa.
KeywordsSenile Plaque Amyloid Protein Anterograde Axonal Transport Cerebrovascular Amyloid Congophilic Angiopathy
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