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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.

Original publication

DOI

10.1002/ana.1254

Type

Journal article

Journal

Annals of neurology

Publication Date

11/2001

Volume

50

Pages

661 - 665

Addresses

Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA. acataldo@mclean.harvard.edu

Keywords

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