P1‐163: Functional and Pathological Characterization of the Brain Microvasculature in a Rat Model of Alzheimer's Disease
Bibliographic record
Abstract
Altered cerebral microvasculature in Alzheimer’s disease (AD) may precede the onset of clinical symptoms. Early detection of AD onset can be advanced through animal models that recapitulate more closely the vascular aspects of clinical AD. The current study examines the microvascular pathologies and the changes in vascular function in response to vasodilatory stimulation in the TgF344 rat model to assess the extent to which this model replicates human AD pathology. Distribution of parenchymal and perivascular Abeta was analyzed using a combination of Thioflavin S and Methoxy-X04 stainings. Immunoblotting was used to measure the protein expression of markers for vascular remodeling, mural cell activity, and blood-brain barrier integrity. We employed in vivo two-photon fluorescent microscopy to image the microvessels of the primary somatosensory cortex in the non-transgenic (nTg) and transgenic (Tg) rats while eliciting global vasodilation through CO2 challenge. The blood flow through arterioles, venules, and capillaries were quantified as time-to-peak (TTP) – time interval between the injection of fluorescent dye and occurrence of peak intensity in select microvessels. In Tg rats, cortical parenchymal plaques concentrated in the lateral-ventral regions while sparsely distributed in the somatosensory and motor regions; perivascular Abeta pathologies appeared primarily in the arterioles of the somatosensory cortex. Protein expressions for desmin and PDGFR-beta, markers of mural cell activity, were increased in the Tg rats while markers for blood-brain barrier integrity did not change significantly. Vascular reactivity of both arterioles and venules was significantly impaired in Tg rats such that TTP shortening due to CO2 challenge was reduced in Tg rats, representing an attenuated response to CO2-induced increase in blood flow. Tg rats also showed wider dispersion of TTP with CO2 challenge in arterioles and capillaries. TgF344 rats captures several key phenotypes of vascular pathology in AD including reduced cerebrovascular reactivity, morphological manifestation of Abeta deposits to the cortical microvasculature, and perturbation of vascular mural cells. The model enables investigation of functional changes in cerebral microvasculature that are clinically relevant toward explaining the mechanism behind corresponding changes in human AD and eventually identifying early indicators of AD prior to its onset.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".