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


Journal article


Ann Neurol

Publication Date





661 - 665


Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apolipoproteins E, Endocytosis, Endosomes, Frontal Lobe, Genetic Predisposition to Disease, Genotype, Humans, Neurons