CSF markers of vascular injury correlate with tau and cognitive decline in early Alzheimer's disease
Bibliographic record
Abstract
INTRODUCTION: Cerebrovascular injury is common in Alzheimer's disease (AD), but its timing in relation to Aβ and tau pathology and cognitive decline remains unclear. METHODS: We measured baseline vascular marker levels in cerebrospinal fluid (CSF) and serum from 75 Alzheimer's Disease Neuroimaging Initiative (ADNI) study participants, stratified into cognitively unimpaired (CU), mild cognitive impairment (MCI), and AD groups (n = 25/group) and investigated associations with disease pathology (CSF and positron emission tomography [PET] amyloid beta [Aβ] and tau) and cognition (Clinical Dementia Rating scale [CDR], Montreal Cognitive Assessment, Mini-Mental State Examination, and Alzheimer's Disease Assessment Scale). RESULTS: CSF markers of endothelial (placental growth factor, angiopoietin 2, angiotensin-converting enzyme-1 [ACE-1]) and pericyte (soluble platelet-derived growth factor receptor beta [sPDGFRβ]) injury were elevated in AD. Most were also higher in CDR 0.5 than CDR 0 and correlated with CSF tau and cognitive impairment in CU and MCI groups, particularly in PET Aβ-positive (Aβ+) participants. Serum sPDGFRβ, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (TIE-2), and ACE-1 correlated with CSF measurements. DISCUSSION: Cerebrovascular injury precedes the development of dementia and, particularly in PET Aβ+ individuals, progresses in close association with CSF tau and cognitive decline. HIGHLIGHTS: We measured the levels of multiple markers of neurovascular injury in serum and CSF taken at baseline from CU, MCI, and AD participants in the ADNI study and investigated associations with CSF and PET markers of disease pathology and with cognitive decline. CSF markers of neurovascular injury, particularly PlGF, are elevated in very early stages of AD, including in MCI and in PET Aβ+ CU individuals. The levels are closely related to CSF t-tau and p-tau and to cognitive decline Levels of only a few neurovascular markers in serum correlate with those in CSF: sPDGFRβ, TIE-2, and ACE-1.
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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 | 0.002 |
| 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 | 0.000 | 0.000 |
| 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".