Association of tau pathology and vascular risk factor burden with longitudinal measures of plasma neurofilament light
Bibliographic record
Abstract
Abstract Background In the context of Alzheimer’s disease (AD), tau pathology is a major driver of the neurodegenerative cascade that ultimately leads to loss of neurons and synapses. In fact, studies have shown that neurodegeneration is more strongly associated with tau pathology than amyloid‐β (Aβ) accumulation. Although plasma neurofilament light (NfL) is a neuroaxonal damage biomarker that currently is in the research spotlight, the factors influencing the association between its longitudinal trajectory and tau pathology remains unclear. Since vascular risk factors (VRFs) present an important role in AD etiology and progression, here we aimed to determine whether tau pathology, in combination with or independently of VRF burden, is associated with longitudinal plasma NfL trajectory. Method We assessed 901 participants [276 CU, 455 MCI and 170 AD] from ADNI with baseline plasma p‐tau181 and [18F]AV45 Aβ‐PET, as well as longitudinal plasma NfL measurements (up to 4 years). Baseline VRF burden was calculated considering the history for cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, stroke or transient ischemic attack, smoking, atrial fibrillation and left ventricular hypertrophy. Individuals were dichotomized as following: elevated VRF burden if ≥2 VRFs (V+), tau positive if plasma p‐tau181 ≥ 17.7 pg/mL (T+) and amyloid positive if global Aβ‐PET SUVR ≥ 1.11 (A+). Subjects who were A‐T+ were excluded. Linear mixed‐effects models (LMMs) were performed to evaluate plasma NfL’s longitudinal trajectories. Result The LMMs demonstrated that tau positivity (T+) was significantly associated with a higher rate of longitudinal increase in plasma NfL levels in comparison to the tau‐negative group (Fig. 1). However, analysis dividing the groups both by tau and VRF burden status demonstrated that the rates of increase in plasma NfL were greater only in the presence of both VRF burden and tau positivity (T+V+; t‐value=2.54, p<0.05), when compared to the reference group (T‐V‐; Fig. 2). Moreover, specific slope‐contrast analyses confirmed that only the T+V+ group presented a clearly separate trajectory. Conclusion Our findings suggest that an elevated VRF burden influences the relation between tau pathology and neurodegeneration in AD.Therefore, tau‐mediated neurodegeneration seems to be most relevant in combination with vascular‐mediated neuroaxonal injury. These findings reinforce the pivotal contribution of vascular pathology to AD development.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".