Title

Cholinergic system during the progression of Alzheimer's disease: Therapeutic implications

Document Type

Article

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 (p75NTR) affinity NGF receptors are crucial factors underlying CBF dysfunction in AD. Drugs that maintain a homeostatic balance between TrkA and p75NTR 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. © 2008 Expert Reviews Ltd.

Keywords

Acetylcholine receptor, Alzheimer's disease, Anticholinesterase, Basal forebrain, Choline acetyltransferase, Cholinergic, Galanin, Gene therapy, Mild cognitive impairment, NGF, Nucleus basalis, p75NTR receptor, Proneurotrophin, Sortilin, Tau, TrkA receptor

Publication Date

11-1-2008

Publication Title

Expert Review of Neurotherapeutics

ISSN

14737175

E-ISSN

17448360

Volume

8

Issue

11

First Page

1703

Last Page

1718

PubMed ID

18986241

Digital Object Identifier (DOI)

10.1586/14737175.8.11.1703

Share

COinS