CSF apolipoprotein B levels predict future visuospatial cognitive decline and synaptic pathology in cognitively unimpaired healthy elderly with a parental history of Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background We examine the role of brain apolipoprotein B (apoB) as a putative CSF indicator of early tau pathology in pre‐symptomatic Alzheimer’s disease (AD). Method Among 129 cognitively unimpaired elderly at increased risk of AD (PREVENT‐AD cohort), we assessed blood and cerebrospinal fluid apoB, apoC3 and apoE protein levels with those of amyloid β42, total tau and phosphorylated tau. We compared results with amyloid‐b (NAV4694) and tau (flortaucipir) positron emission tomography uptake and cognitive assessment alterations over 6‐8 years. Tangle and plaque pathologies were contrasted with cortical APOB, APOC3 and APOE mRNA levels in 240 autopsied subjects enrolled in the Religious Orders Study and Memory and Aging Project (ROSMAP) studies with diagnoses of cognitively unimpaired, mild cognitive impairment, or AD. Result Among cognitively unimpaired participants, we observed significant correlations between baseline CSF, but not blood, apoB levels and both CSF t‐tau (R2 = 0.23, P < 0.0001) and P‐tau (R2 = 0.28, P < 0.0001). Similar associations were observed when using PET flortaucipir‐binding in entorhinal, parahippocampal and fusiform regions. No association was detected between CSF apoB and CSF Aβ42 levels or cerebral Ab deposition. Baseline CSF apoB levels were associated with visuospatial cognitive decline over the course of 6‐8 years (R2 = 0.13, P < 0.02) and alterations in several synaptic proteins in the CSF. Contribution from peripheral apoB was found to be negligible. In ROSMAP, APOB gene expression failed to correlate with either tangle pathology or amyloid plaque deposition. Conclusion CSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at‐risk individuals predisposed to develop visuospatial cognitive decline over time.
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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 | 0.001 |
| 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".