Changes in Alzheimer's disease‐associated biomarkers in COVID‐19 patients presenting neurological symptoms
Bibliographic record
Abstract
BACKGROUND: COVID-19 induces acute and long-term neurological symptoms. Alzheimer's disease (AD) is a risk factor for severe COVID-19, and COVID-19 survivors may experience cognitive decline. Because inflammation plays a significant role in both diseases, links between COVID-19 and AD have been hypothesized. However, it is unknown if COVID-19 patients with neurological disturbance present molecular alterations related to AD pathology. Identifying possible molecular links between COVID-19 and AD would improve patient follow-up and late-onset disease prevention. Here, we tested the possibility that COVID-19 neurological patients present early AD-related molecular neuropathological alterations. METHOD: In a retrospective analysis, we compared AD-related cerebrospinal fluid (CSF) biomarkers of amyloid-beta (Ab) proteinopathy (Ab42/40), tauopathy (phosphorylated Tau, pTau181), and total Tau from controls (n = 36), amnestic mild cognitive impairment (aMCI, n = 19), AD (n = 20), and COVID-19 patients presenting important neurological alterations at hospitalization (n = 35). CSF biomarkers were correlated with systemic and central nervous system inflammation markers. In a prospective cohort (n = 41), we evaluated plasma Ab42, Ab40, and Tau longitudinal changes up to one-year post-COVID using SIMOA. Plasma biomarkers were correlated with cognitive outcomes. The Brazilian Ministry of Health and IDOR approved the study protocol. RESULT: We found that, at hospitalization, severe COVID-19 patients with neurological symptoms presented elevated CSF Tau, like AD patients. However, we did not detect changes in CSF Ab42/Ab40, pTau-181/Ab42, or Tau/Ab42 ratios. CSF pro-inflammatory cytokine IL6 levels and AD-related biomarkers (Tau, pTau181, Tau/Ab42, pTau-181/Ab42) positivelycorrelated with systemic inflammatory index (SII). Up to one-year post-COVID, we found that plasma Tau/Ab42 selectively increased in patients with cognitive deficits. Plasma Tau longitudinal changes were most influenced by COVID-19 disease severity (negatively) and SII (positively) at hospitalization and the presence of post-COVID cognitive deficits (positively). CONCLUSION: Collectively, our findings put inflammation as a primary correlate of acute and persistent AD-related molecular changes in COVID-19 patients, urging careful follow-up of COVID-19 survivors with lingering inflammation or cognitive symptoms for possible risk of future AD.
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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 | 0.001 | 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".