Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders

The endocytic pathway is important in amyloid precursor protein (APP) proce ssing and beta -amyloid formation. Our studies have shown that endocytic pa thway activation is a prominent and early feature of neurons in vulnerable regions of the brain in sporadic Alzheimer's disease. We report that endocy tic pathway abnormalities are present not only in neurons, but in cerebral endothelia in Alzheimer's disease caused by certain APP mutations. The pres ence or absence of endocytic abnormalities distinguish subtypes of familial Alzheimer's disease linked to APP mutations from presenilin mutations, sup porting the notion that different cellular pathways are involved in the alt ered processing of APP leading to increased beta -amyloid generation in cer tain of these different Alzheimer's disease subtypes.