Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies

@article{Auld2002AlzheimersDA,
  title={Alzheimer’s disease and the basal forebrain cholinergic system: relations to $\beta$-amyloid peptides, cognition, and treatment strategies},
  author={Daniel Auld and Tom J. Kornecook and Stéphane Bastianetto and Rémi Quirion},
  journal={Progress in Neurobiology},
  year={2002},
  volume={68},
  pages={209-245}
}

Basal Forebrain Cholinergic Dysfunction in Alzheimer’s Disease – Interrelationship with β-amyloid, Inflammation and Neurotrophin Signaling

  • R. Schliebs
  • Biology, Psychology
    Neurochemical Research
  • 2005
TLDR
Understanding the molecular mechanisms underlying the interrelationship between cortical cholinergic dysfunction, β-amyloid formation and deposition, as well as local inflammatory upregulation, would allow to derive potential treatment strategies to pharmacologically intervene in the disease-causing signaling cascade.

The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease

TLDR
Understanding the molecular mechanisms underlying the interrelationship between cortical cholinergic dysfunction, β-amyloid formation and deposition, and tau pathology in Alzheimer’s disease, would allow to derive potential treatment strategies to pharmacologically intervene in the disease-causing signaling cascade.

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.

Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: A role for intraneuronal amyloid

Amyloid β-Peptide and Central Cholinergic Neurons: Involvement in Normal Brain Function and Alzheimer’s Disease Pathology

TLDR
Alzheimer’s disease is characterized by a global deterioration of intellectual function that includes an amnesic type of memory impairment, deterioration of language, and visuospatial deficits, and motor and sensory abnormalities are uncommon until the late phases of the disease.

Alzheimer’s Disease Amyloid β-Protein and Synaptic Function

TLDR
There is growing evidence to support the view that NMDA and possibly nicotinic receptors are critically involved in mediating the disruptive effect of Aβ and that targeting muscarinic receptors can indirectly modulate Aβ’s actions, with particular emphasis on the different roles of glutamatergic and cholinergic mechanisms.

INTERACTIONS OF CHOLINERGIC INNERVATION AND SOLUBLE AB42 PEPTIDE METABOLISM IN THE HIPPOCAMPUS

TLDR
The data indicate that cholinomimetic therapies could prove valuable in suppressing increases in potentially neurotoxic soluble Aβ levels, and provide a model for evaluating in vivo the relationship between cholinergic function and amyloid metabolism.

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

TLDR
Cholinergic abnormalities may also contribute to noncognitive behavioral abnormalities as well as the deposition of toxic neuritic plaques in AD and cholinergic-based strategies will likely remain valid as one approach to rational drug development for the treatment of AD other forms of dementia.
...

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TLDR
Using in vivo rodent models, several cholinergic enhancement strategies have been tested and proven to be effective in alleviating lesion-induced cognitive deficits, including neuropharmacological approaches (acetylcholinesterase inhibitors), neurotrophic factor administration (nerve growth factor), and transplantation of Cholinergic-enriched fetal grafts.

Acetylcholine and Alzheimer's Disease

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TLDR
A number of key questions specifically relating to the cholinergic involvement in Alzheimer's disease are considered and are already being answered both within and outside the immediate area of investigation.

Cholinergic Changes in the APP23 Transgenic Mouse Model of Cerebral Amyloidosis

TLDR
The present study examines the cholinergic alterations in amyloid precursor protein transgenic mice (APP23), a mouse model of cerebral β-amyloidosis, and concludes that the severe Cholinergic deficit in AD is caused by both the loss of cholinery basal forebrain neurons and locally by cerebral amyloidsosis in the neocortex.

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TLDR
It is shown that Aβ peptides, under acute conditions, can decrease endogenous ACh release and the uptake of choline but exhibit no effect on ChAT activity, suggesting that the preferential vulnerability of basal forebrain cholinergic neurons and their projections in AD could relate, at least in part, to their sensitivity to A β peptides.
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