The Role of Synaptopathy in Alzheimer's Disease: A Review of Key Transgenic Mouse Models
Bibliographic record
Abstract
Introduction: Long-term potentiation (LTP) and its counterpart, long-term depression (LTD), are considered the cellular basis underpinning learning and memory. Impairments in these processes are associated with neurodegenerative diseases such as Alzheimer’s disease (AD). These impairments are emergent during the onset of AD, suggesting a critical role in the pathophysiology of AD. Popular transgenic AD models, such as 5xFAD, 3xTg, Tau MAPT P301L, and APPswe/PSEN1dE9 demonstrate changes in synaptic plasticity early during their lifespan. This systematic review aims to investigate localization and onset of synaptopathy associated with AD. Methods: A comprehensive literature search was conducted using PubMed (Medline) to identify common features across models associated with synaptic plasticity. Papers were screened through two stages. The first stage involved establishing a set of criteria, including search terms. The second stage centered on ensuring chosen studies focused on synaptopathy and utilized the models selected. Results: Eight studies were selected across the four transgenic mouse models that established onset and localization of synaptopathy in AD pathophysiology. In the majority of studies, impairments in synaptic plasticity were first found in the CA1 region of the hippocampus. Moreover, onset of these impairments developed prior to onset of neuropathology and behavioral or cognitive deficits. Impairments in synaptic plasticity included inhibition of glutamate release, decreased cell excitability, dendritic atrophy and impaired receptor signaling. Discussion: The results of this review suggest localization of synaptic plasticity impairments to the CA1 region preceding development of neuropathologies such as amyloid or tau aggregation and cognitive deficits. This indicates an early and critical role of synaptopathy at the CA1 region, implicating it as a potential causal factor in the pathophysiology of AD. Conclusion: While the FAD models evaluated in this review implicate changes in synaptic plasticity within AD, they are not representative of late onset AD (LOAD), the prevalent form of the disease in the population. Currently research using LOAD models is limited, causing reliance on FAD models for the study of AD. As prevalence of AD increases in the population, it is essential that new models of LOAD are developed and studied to further current understandings of AD pathophysiology.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.014 | 0.011 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".