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
Citations
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Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model.
Jennifer H.K. Choi,Jason D. Berger,Matthew J. Mazzella,Jose Morales-Corraliza,Anne M. Cataldo,Anne M. Cataldo,Ralph A. Nixon,Ralph A. Nixon,Stephen D. Ginsberg,Efrat Levy,Paul M. Mathews +10 more
TL;DR: Brain levels of both Aβ40 and Aβ42 were not increased in Ts65Dn mice compared with diploid mice at all ages examined, suggesting multiple mechanisms contribute to the regulation towards diploids levels of APP metabolites in the Ts 65Dn mouse brain.
Journal ArticleDOI
Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice.
Sylvia E. Perez,Bin He,Nadeem Muhammad,Kwang-Jin Oh,Margaret Fahnestock,Milos D. Ikonomovic,Elliott J. Mufson +6 more
TL;DR: It is demonstrated that cholinotrophic alterations in 3xTg-AD mice are age- and gender-dependent and more pronounced in the hippocampus, a structure more severely affected by Aβ plaque pathology.
Journal ArticleDOI
The functional neurophysiology of the amyloid precursor protein (APP) processing pathway
TL;DR: Changes to clinical neurophysiology seen in AD patients are outlined before discussing functional changes in mouse models of AD which range from changes to basal synaptic transmission and synaptic plasticity through to abnormal synchronous network activity.
Journal ArticleDOI
Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AβPP(L/S) transgenic mice.
Thuy-Vi V. Nguyen,Lin Shen,Lilith Vander Griend,Lisa N. Quach,Nadia P. Belichenko,Nay Saw,Tao Yang,Mehrdad Shamloo,Tony Wyss-Coray,Stephen M. Massa,Frank M. Longo +10 more
TL;DR: A role for p75NTR ligands in preventing fundamental tau-related pathologic mechanisms in AD is supported, and the development of these small molecules as a new class of therapeutic compounds is validated.
Journal ArticleDOI
Management of mild cognitive impairment (MCI): The need for national and international guidelines.
Siegfried Kasper,Christian Bancher,Anne Eckert,Hans Förstl,Lutz Frölich,Jakub Hort,Amos D. Korczyn,Reto W. Kressig,Oleg Levin,María Sagrario Manzano Palomo +9 more
TL;DR: MCI is recognised as an important treatment target and some recent national guidelines have considered symptomatic treatment recommendations for MCI, however, more needs to be done, especially at an international level.
References
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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
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