Intracellular Amyloid-β in the Normal Rat Brain and Human Subjects
Bibliographic record
Abstract
Abstract Amyloid-beta (Aβ) is a normal product of neuronal activity, and the two most common variants are 40 or 42 residues long. Of these, the 42 residue-version (Aβ42) is normally less abundant but more prone to self-aggregate, and is thought to cause Alzheimer’s disease (AD). Much knowledge about AD-pathogenesis comes from the study of rodents made to model aspects of the disease by expressing AD-relevant human transgenes, like human amyloid precursor protein (APP) containing mutations that drive up Aβ production or increase the Aβ42/40 ratio and thereby causes AD. Yet, when it comes to the normal expression of Aβ42 in rodent brains, surprisingly little is known. Here we characterize the expression of Aβ42 throughout the brain of normal, outbred Wistar rats, including animals from 3-18 months of age. We find that intracellular Aβ42 (iAβ42) is present in neurons located throughout the brain at all ages of normal Wistar rats, but that the levels vary greatly between brain regions. In cortex, we observe the highest levels of iAβ42 in neurons that are part of layer II of the entorhinal cortex (EC), along with neurons in the hippocampus, closely followed by neurons in the somatosensory cortex. Among subcortical structures, we observe the highest levels iAβ42 in the locus coeruleus. In order to explore whether the striking presence of iAβ42 in rat EC also holds true in human subject free of neurological disease, we examined EC of six such cases ranging from ages 20-88 years. In all six cases, we find that iAβ42 is present in EC layer II-neurons. Our findings support two conclusions about iAβ42. First, iAβ42 is present in neurons of wild-type Wistar rats and is restricted to the same structures where iAβ accumulates, and Aβ-plaques form, in a much used AD model based on Wistar rats (the McGill-R-Thy1-APP rat model). The difference between wild-type Wistar rats and these AD model rats, with respect to Aβ42, is therefore a quantitative one rather that a qualitative one. This indicates that the McGill rat model in fact models the underlying wild-type neuronal population-specific vulnerability to Aβ42-accumulation. Second, because the McGill rat model closely mimics the human AD-associated spatiotemporal sequence of amyloid plaque deposition, this model may offer a useful representation of the pre-plaque neuronal accumulation of iAβ42. Our findings in human cases are in line with prior findings, and substantiate the notion that neurons in layer II of EC are vulnerable to accumulation of iAβ42.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".