title: Cholinergic system during the progression of Alzheimer's disease: therapeutic implications.
abstract: Alzheimer's disease (AD) is characterized by a progressive phenotypic downregulation of markers within cholinergic basal forebrain (CBF) neurons, frank CBF cell loss and reduced cortical choline acetyltransferase activity associated with cognitive decline. Delaying CBF neurodegeneration or minimizing its consequences is the mechanism of action for most currently available drug treatments for cognitive dysfunction in AD. Growing evidence suggests that imbalances in the expression of NGF, its precursor proNGF and the high (TrkA) and low (p75(NTR)) affinity NGF receptors are crucial factors underlying CBF dysfunction in AD. Drugs that maintain a homeostatic balance between TrkA and p75(NTR) may slow the onset of AD. A NGF gene therapy trial reduced cognitive decline and stimulated cholinergic fiber growth in humans with mild AD. Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. emufson@rush.edu
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Scott E
authors.initials: SE
authors.lastname: Counts
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Perez
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor