Plasma biomarkers across the spectrum of Alzheimer’s and Parkinson’s disease: Association with cortical thickness and cognitive dysfunction
Bibliographic record
Abstract
Abstract Background Plasma biomarkers of phosphorylated‐tau(p‐tau), astrocytosis and axonal damage offer a reliable means of identifying and measuring multiple pathological processes in‐vivo. How these biomarkers are associated with cortical brain structure and cognition within, and across, disorders is unclear. Leveraging the Ontario Neurodegenerative Disease Research Initiative, we examined the cross‐sectional association between plasma biomarkers, cortical thickness, and multi‐domain cognition. Method 290 participants diagnosed with AD or PD (in accordance with clinical guidelines) and healthy controls (HC) were included (MeanAge = 68.96;[41% women; 35% APOE4carriers]). Four groups were formed: i)AD with mild cognitive impairment or dementia(ADMCI/ADD;N = 121), ii)PD with MCI or dementia(PDMCI/PDD;N = 78), iii)PD with normal cognition(PD‐NC;N = 43) and HC(N = 44; Table1). Plasma measures of p‐tau181‐UGOT, Neurofilament light chain (NfL) and GFAP, alongside FreeSurfer‐derived cortical thickness were included. A neuropsychological battery was administered. All models were adjusted for age, sex, and education. Result There was an effect of diagnostic group on global cortical thickness, with PD‐NC, ADMCI/ADD and PDMCI/ADD exhibiting a significant reduction relative to HC(Fig1A). Regional patterns of brain atrophy were significantly associated in ADMCI/ADD and PDMCI/ADD(Fig1B). Across groups, p‐tau181, GFAP and to a lesser extent NfL, were associated with cortical thinning, particularly in lateral temporal and medial parietal regions (Fig2A). Unlike global thickness, ADMCI/ADD and PDMCI/PDD, but not PD‐NC, showed reduced thickness in the regions associated with p‐tau181, GFAP and NfL (Fig2B). Diagnostic group*GFAP/NfL/ptau181 interactions were not significant. Mediation analysis showed the cortical thinning in lateral temporal and medial parietal regions mediated between 33% to 40% of association between p‐tau181 and delayed memory. Similarly, thinning in these areas mediated 22% to 33% of the relationship between GFAP and executive function(Fig2C). Conclusion We conclude that there is a similar pattern of gray matter loss in MCI/Dementia due to AD and PD. Higher concentrations of plasma p‐tau181 and GFAP are associated with poorer memory and executive function, in part through cortical thinning in lateral temporal and medial parietal regions. In conclusion, pathological processes related to the deposition of amyloid and tau, as well as astrogliosis, may co‐exist across cognitively impaired individuals with AD and PD. This is consistent with autopsy findings showing that AD pathology is present in 33‐60% of PD patients.
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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 | 0.001 | 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) | 0.002 | 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".