The role of the p75 neurotrophin receptor in cholinergic dysfunction in Alzheimer's disease.
Degeneration of basal forebrain cholinergic neurons is a common feature of Alzheimer's disease and is proposed to be an early and key event in the condition's etiology. This review discusses recent findings that strongly link the p75 neurotrophin receptor (p75(NTR)) to both cholinergic neuron degeneration and the production of toxic forms of amyloid-beta (Abeta), which is found deposited as amyloid plaques in the brains of Alzheimer's disease patients. Although elucidating the underlying molecular mechanisms and the clinical significance of these findings will require further experimentation, a number of possible scenarios and future research directions are presented.
Coulson
E J
EJ
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. e.coulson@uq.edu.au
May
L M
LM
Sykes
A M
AM
Hamlin
A S
AS
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000378:metabolism*; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000172:deficiency; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D000109:Acetylcholine