Cholinergic system during the progression of Alzheimer's disease: therapeutic implications.
TLDR
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.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.read more
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References
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Journal ArticleDOI
Mild cognitive impairment as a diagnostic entity
TL;DR: It is suggested that the diagnosis of mild cognitive impairment can be made in a fashion similar to the clinical diagnoses of dementia and AD, and an algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI.
Journal ArticleDOI
Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.
Bengt Winblad,Katie Palmer,Miia Kivipelto,Vesna Jelic,Laura Fratiglioni,Lars-Olof Wahlund,Agneta Nordberg,Lars Bäckman,Marilyn S. Albert,Ove Almkvist,Hiroyuki Arai,Hans Basun,Kaj Blennow,M. J. de Leon,Charles DeCarli,Timo Erkinjuntti,Ezio Giacobini,Caroline Graff,John Hardy,Clifford R. Jack,Anthony F. Jorm,Karen Ritchie,C M van Duijn,Pieter Jelle Visser,Ronald C. Petersen +24 more
TL;DR: A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics.
Journal ArticleDOI
Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
Robert D. Terry,Eliezer Masliah,David P. Salmon,Nelson Butters,Richard DeTeresa,Robert Hill,Lawrence A. Hansen,Robert Katzman +7 more
TL;DR: Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.
Journal ArticleDOI
Selective loss of central cholinergic neurons in alzheimer's disease
Peter Davies,A.J.F. Maloney +1 more
Journal ArticleDOI
Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
TL;DR: Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.
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