Amyloid-β and Hyperphosphorylated tau SynergyDrives Clinical Progression in Individuals with Mild Cognitive Impairment (P2.228)
Bibliographic record
Abstract
OBJECTIVE: Our objective was to test the hypothesis that neuropsychological and clinical decline in patients with mild cognitive impairment is dependent on the synergism between brain amyloid-β deposition and tau hyperphosphorylation. BACKGROUND: Recent literature proposes that the synergism between amyloidosis and neurodegeneration determines Alzheimer’s disease progression. DESIGN/METHODS:In order to test this hypothesis, we assessed individuals with amnestic mild cognitive impairment (n=314) who underwent [18F]florbetapir positron emission tomography, cerebrospinal fluid phosphorylated tau measurements and cognitive testing assessments at baseline and at 2 years. Regression models and analysis of covariance assessed changes in cognitive tests as a function of baseline imaging and fluid biomarker concentrations. RESULTS: We found that patients with abnormal baseline brain amyloid-β load plus cerebrospinal phosphorylated tau had the highest rate of cognitive and clinical decline, as compared with individuals with one or no biomarker abnormalities (P<0.05). Additionally, regression models revealed that amyloid-β and phosphorylated tau biomarkers’ synergistic interaction best predicted cognitive decline and clinical progression to Alzheimer’s disease dementia, as compared to the sum of their individual effects (P<0.05). Furthermore, stratified regression analysis showed that the magnitude of amyloid-β and phosphorylated tau biomarkers predicted cognitive decline and clinical progression to dementia only in the presence of abnormal baseline amyloid-β load plus tau phosphorylation (P<0.05). Interestingly, neuropsychological and clinical trajectories did not differ between individuals with mild cognitive impairment having elevated phosphorylated tau but normal amyloid-β deposition (suspected nonamyloid pathology) and biomarker negative individuals. CONCLUSIONS: Together, the present results further support the concept that clinical progression of Alzheimer’s disease is driven by a synergism between amyloidosis and neurodegeneration, rather than their respective independent or additive effects. Evidence for the coexistence of abnormal brain amyloid-β deposition and cerebrospinal fluid phosphorylated tau might constitute a valuable strategy for population enrichment in trials focusing on individuals with amnestic mild cognitive impairment.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".