Axonal Lysosome dysfunction in Alzheimer’s disease

Excess levels of the amyloid β (Aβ) peptide and the aggregation of the Aβ peptide within extracellular amyloid plaques are defining features of Alzheimer’s disease brain pathology. A poorly understood aspect of these amyloid plaques is the massive abundance of lysosomes that selectively accumulate within swollen neuronal axons that pass close to them. We are using mouse models of Alzheimer’s disease to investigate the mechanisms that give rise to the abnormal abundance and localization of lysosomes in Alzheimer’s disease neurons with the expectation that such studies will enhance understanding of how neurons regulate lysosome abundance and localization and how modulation of lysosome function could have therapeutic benefits in the treatment of Alzheimer’s disease.