Mitochondrial complex I abnormalities underlie neurodegeneration and cognitive decline in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background and purpose Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study was to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggregation or glucose metabolism and brain atrophy in patients with mild AD using positron emission tomography (PET). Methods Amyloid‐ and tau‐positive symptomatic AD patients with clinical dementia rating 0.5 or 1 ( N = 30; mean age ± standard deviation: 71.8 ± 7.6 years) underwent magnetic resonance imaging and PET scans with [ 18 F]2‐tert‐butyl‐4‐chloro‐5–2H‐pyridazin‐3‐one (BCPP‐EF), [ 11 C]Pittsburgh Compound‐B (PiB) and [ 18 F]fluorodeoxyglucose (FDG) to assess brain atrophy, mitochondrial complex I dysfunction, amyloid deposition, and glucose metabolism, respectively. Local cortical associations among these biomarkers and gray matter volume were evaluated with voxel‐based regressions models. Results [ 18 F]BCPP‐EF standardized uptake value ratio (SUVR) was positively correlated with [ 18 F]FDG SUVR in the widespread brain area, while its associations with gray matter volume were restricted to the parahippocampal gyrus. Reductions in [ 18 F]BCPP‐EF SUVR were associated with domain‐specific cognitive performance. We did not observe regional associations between mitochondrial dysfunction and amyloid burden. Conclusions In symptomatic cases, although mitochondrial complex I reduction is linked to a wide range of downstream neurodegenerative processes such as hypometabolism, atrophy, and cognitive decline, a link to amyloid was not observable. The data presented here support [ 18 F]BCPP‐EF as an excellent imaging tool to investigate mitochondrial dysfunction in AD.
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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 | 0.001 |
| 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".