Dialogues Clin Neurosci. 2000 Jun;2(2):101-10.

Fleshing out the amyloid cascade hypothesis: the molecular biology of Alzheimer's disease.

Dialogues in clinical neuroscience

S Lovestone

PMID: 22033981 PMCID: PMC3181594

Abstract

Alzheimer's disease (AD) is a disorder of two pathologies- plaques and tangles. The former have as a key constituent amyloid protein and the latter the microtubule-associaied protein tau. Genetics has demonstrated that changes in either protein are sufficient to cause dementia. The amyloid cascade hypothesis proposes that plaque-related changes precede tangle-related changes and positions amyloid as central to the degeneration of AD. All the evidence suggests this is correct, including evidence that presenil ins alter the processing of the amyloid precursor protein and evidence that disrupting the normal properties of tau underlies the related froniotemporal dementias. The amyloid cascade hypothesis has provided the basis for nearly a decade of intensive basic science - the skeleton of that hypothesis can now be fleshed out, and confidence is growing that this will result in useful disease-modifying therapies in the future.

Keywords: APP; Alzheimer's disease; GSK-3; Notch; amyloid; presenilin; tau; tauopathy

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