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The molecular significance of amyloid β-peptide for Alzheimer's disease

  • Neurobiological Substrates of Clinical Deficits in Alzheimer's Disease
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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Alzheimer's disease is the most common form of dementia. Although the majority of the cases occur sporadically, in some rare cases Alzheimer's disease is genetically inherited. Pathologically, Alzheimer's disease is characterized by the accumulation of senile plaques within the extracellular space of brain regions known to be important for intellectual functions. In addition to senile plaques, deposits of identical biochemical composition are found in the walls of meningeal and cerebral blood vessels. Senile plaques are surrounded by degenerating neurons indicating a toxic interference of amyloid plaques with neurons. The major component of senile plaques is the 4 kDa amyloid β-peptide. This peptide has been shown to exhibit neurotoxic properties when added to cultured neurons, or injected into rat brains. Amyloid β-peptide is derived from a high molecular weight precursor, the β-amyloid precursor protein, by proteolytic processing. Mutations responsible for the early onset of Alzheimer's disease in some families are found within the gene coding for the β-amyloid precursor protein. These mutations strongly influence the generation of amyloid β-peptide resulting in a significant overproduction of the peptide or the generation of elongated forms which are known to aggregate and precipitate much faster. Moreover, mutations found in other genes known to cause early onset of Alzheimer's disease have been shown to interfere directly with the production or precipitation of amyloid β-peptide.

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  1. Department of Molecular Biology, Central Institute of Mental Health, J5, D-68159, Mannheim, Germany

    Christian Haass

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Haass, C. The molecular significance of amyloid β-peptide for Alzheimer's disease. Eur Arch Psychiatry Clin Nuerosci 246, 118–123 (1996). https://doi.org/10.1007/BF02189111

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