Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications
Year: 2008
Type: review
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.
Institutions: Rush University Medical Center, New York University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Neurobiology of Mild Cognitive Impairment in the Elderly, Pathological and Functional Impact of Tauopathy in vivo, Rush Alzheimer's Disease Core Center, G6274562036, Cellular and Molecular Medial Temporal Lobe Pathology in Elderly PreMCI subjects, Proteomics of mild cognitive impairment in the elderly, Anatomic, Physiologic, and Cognitive Pathology of AD, Galanin in Alzheimer's Disease, Cell and Molecular Pathobiology of Alzheimer's Disease
OpenAlex ID: W2097391583