Axonopathy and Transport Deficits Early in the Pathogenesis of Alzheimer's Disease
Top Cited Papers
- 25 February 2005
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 307 (5713) , 1282-1288
- https://doi.org/10.1126/science.1105681
Abstract
We identified axonal defects in mouse models of Alzheimer's disease that preceded known disease-related pathology by more than a year; we observed similar axonal defects in the early stages of Alzheimer's disease in humans. Axonal defects consisted of swellings that accumulated abnormal amounts of microtubule-associated and molecular motor proteins, organelles, and vesicles. Impairing axonal transport by reducing the dosage of a kinesin molecular motor protein enhanced the frequency of axonal defects and increased amyloid-β peptide levels and amyloid deposition. Reductions in microtubule-dependent transport may stimulate proteolytic processing of β-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease.Keywords
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