Role of amyloid β peptides in the regulation of central cholinergic function and its relevance to Alzheimer's disease pathology
Bibliographic record
Abstract
Abstract The neuropathological features associated with Alzheimer's disease (AD) brain include the presence of extracellular neuritic plaques composed of amyloid β protein (Aβ), intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, and the loss of basal forebrain cholinergic neurons that innervate regions such as the hippocampus and the cortex. Studies of the pathological changes that characterize AD and several other lines of evidence indicate that Aβ accumulation in vivo may initiate and/or contribute to the process of neurodegeneration and thereby the development of AD. However, the mechanisms by which Aβ peptide influences/causes degeneration of the basal forebrain cholinergic neurons and/or the cognitive impairment characteristic of AD remain obscure. A number of recent studies indicate that physiological concentrations of soluble Aβ‐related peptides, under acute conditions, can negatively regulate various steps of acetylcholine (ACh) synthesis and release without inducing any apparent toxicity, suggesting a possible neuromodulatory role for the peptide in the regulation of central cholinergic functions. Chronic exposure to μM concentrations of Aβ peptides, on the other hand, evokes toxicity in cholinergic neurons, possibly via hyperphosphorylation of tau protein. Activation of selected cholinergic receptors has been shown to influence the processing of amyloid precursor protein as well as modulation of tau phosphorylation. More recently, a direct interaction between nicotinic ACh receptor and Aβ peptides have been demonstrated using a variety of approaches. This review focuses on the role of Aβ‐related peptides in the regulation of function/survival of central cholinergic neurons and its relevance to the cholinergic deficits observed in AD brains. Drug Dev. Res. 56:248–263, 2002. © 2002 Wiley‐Liss, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".