Mathews Lab

The group studies the cell biological events leading to neurodegenerative diseases in vitro using cultured cell systems and in vivo using transgenic mouse models of AD-related pathology as well as the growing number of mouse models, such as Down syndrome models, that highlight the mechanistic linkage between neurodevelopmental and neurodegenerative disorders.

Our focus is on understanding how alterations in intracellular vesicle trafficking and the expression and movement of specific membrane proteins at the plasma membrane and through the endosomal-lysosomal pathway impact the progression of neurodegenerative and neurodevelopmental disorders. This includes modulation of amyloid precursor protein (APP) intracellular distribution and trafficking, the proteolytic systems that contribute to its metabolism, the impact of disease risk-factors on these events and systems, and, ultimately, the role various APP metabolites play both in the normal function of the brain and during pathological processes.

In addition to examining disease-driving changes in neuronal endocytosis and APP metabolism in mouse models of Down syndrome and other AD-related models, the group’s in vivo studies involve the analysis of a number of β-amyloid depositing mice and the relationship between alterations in Aβ production (or the production of particular Aβ-peptides) and pathology, and we have developed extensive capabilities to analyze APP metabolites levels and metabolism in the mouse brain.