Sex differences in the levels of key mitochondrial markers in subjects with mild cognitive impairments and Alzheimer’s disease
Bibliographic record
Abstract
Introduction The lack of accessible plasma biomarkers to identify target populations limits the promise of precision medicine for Alzheimer’s Disease (AD). Amnestic mild cognitive impairment (aMCI) is an important risk for AD and often occurs years before the onset of AD. Objectives Based on an emerging mechanistic model of mitochondrial mechanisms of brain plasticity, we studied the role of acetylcarnitine and free-carnitine levels assayed in plasma as potential markers of cognitive dysfunction in subjects with aMCI or early-AD. Methods We used available samples from two independent cohorts well characterized for clinical and neuropsychological characteristics together with ultraperformance liquid chromatography-tandem mass spectrometry and computational approaches. Cerebrospinal fluid (CSF) measures of b-amyloid accumulation and t-Tau levels were also available and used in computational modeling. Results Within the primary cohort, our data showed decreased levels of carnitine in relation to cognitive function as assessed by using the Mini Mental Status Exam (MMSE) in women but not men with CI as compared to age- and sex-matched HC. Furthermore, the magnitude of carnitine deficiency reflected the severity of cognitive dysfunction in a sex-specific manner (women: p = 0.015; men: p = 0.441). Our data also replicated the prior finding of decreased LAC levels in both women and men with AD, supporting the robustness of the study samples assayed in our new study. Using computational approaches, we found that the integration of these mitochondrial measures with canonical CSF biomarkers improves diagnostic accuracy. A second cohort provides a validation of the sex-specific relationship between free-carnitine deficiency and the severity of cognitive dysfunction. Conclusions Taken together with prior mechanistic studies in rodents, the current findings support future research on the development of individualized treatment models targeting sex-specific changes in mitochondrial metabolism. Disclosure of Interest None Declared
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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 teacher head, 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".