Abeta1-42 promotes cholinergic sprouting in patients with AD and Lewy body variant of AD.
BACKGROUND
The neurodegenerative process in Alzheimer's disease (AD) and in the Lewy body variant of AD (LBV) patients is characterized by cholinergic dysfunction and deposition of amyloid beta-peptide (Abeta) 1-40 and 1-42; however, the differential effects of Abeta species on the cholinergic system are not completely clear.


OBJECTIVE
To better understand the relationship between levels of Abeta1-40 and 1-42 on cholinergic deficits in AD and LBV patients.


METHODS
Levels of choline acetyltransferase (ChAT) activity and ChAT immunoreactivity in the plaques in the frontal cortex of patients with AD and LBV were correlated with Abeta1-42 and 1-40 levels determined by ELISA and with neuropathologic and neurologic markers.


RESULTS
Although the overall levels of ChAT activity were reduced in AD and LBV cases, there was a direct correlation with Abeta1-42 levels. Furthermore, patients with high Abeta1-42 levels had more abundant cholinergic dystrophic neurites in the plaques than cases with lower Abeta1-42.


CONCLUSIONS
Abeta1-42 may also trigger cholinergic dysfunction by promoting aberrant neuritic sprouting.
Masliah
E
E
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA. emasliah @ucsd.edu
Alford
M
M
Adame
A
A
Rockenstein
E
E
Galasko
D
D
Salmon
D
D
Hansen
L A
LA
Thal
L J
LJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000502:physiology*; D020532:Basal Nucleus of Meynert / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002799:Cholinergic Fibers / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000473:pathology*; D019922:GAP-43 Protein / Q000032:analysis; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D016501:Neurites / Q000648:ultrastructure; D016874:Neurofibrillary Tangles; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000032:analysis / Q000502:physiology*; D058225:Plaque, Amyloid / Q000737:chemistry; D016037:Single-Blind Method
D016229:Amyloid beta-Peptides; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D002795:Choline O-Acetyltransferase