Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders.
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.
Cataldo
A
A
Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA. acataldo@mclean.harvard.edu
Rebeck
G W
GW
Ghetri
B
B
Hulette
C
C
Lippa
C
C
Van Broeckhoven
C
C
van Duijn
C
C
Cras
P
P
Bogdanovic
N
N
Bird
T
T
Peterhoff
C
C
Nixon
R
R
D000544:Alzheimer Disease / Q000145:classification* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000473:pathology; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E