Brain atrophy progression in Parkinson’s disease is shaped by connectivity and local vulnerability
Bibliographic record
Abstract
Abstract Atrophy in multiple brain regions has been reported in the early stages of Parkinson’s Disease, but there have been few longitudinal studies. How intrinsic properties of the brain, such as anatomical connectivity, local cell type distribution and gene expression combine to determine the pattern of disease progression remains unknown. One hypothesis proposes that the disease stems from prion-like propagation of misfolded alpha-synuclein via the connectome that might cause varying degrees of tissue damage based on local properties. Here we used MRI data from the Parkinson Progression Markers Initiative to test this model by mapping the progression of brain atrophy over one, two and four years and relating it to brain structural and functional connectivity, cell type expression and gene ontology enrichment analyses. In this longitudinal study, we derived atrophy progression maps for the three time points using deformation-based morphometry applied to T1-weighted MRI from 74 de novo Parkinson’s Disease patients (50 Men: 24 Women) and 157 healthy control participants (115 Men: 42 Women). After regressing out the expected age and sex effects associated with normal aging, we found that atrophy significantly progressed over two and four years in the caudate, nucleus accumbens, hippocampus, and the temporal, parietal, occipital and posterior cingulate cortex. This progression was shaped by both structural and functional brain connectivity. Also, the progression of atrophy was more pronounced in regions with a higher expression of genes related to synapses and was related to the prevalence of oligodendrocytes and endothelial cells. In sum, we demonstrate that the progression of atrophy in Parkinson’s Disease is in line with the prion-like propagation hypothesis of alpha-synuclein and provide evidence that synapses may be especially vulnerable to synucleinopathy. In addition to identifying vulnerable brain regions, this study reveals different factors that may be implicated in the neurotoxic mechanisms leading to progression in Parkinson’s Disease.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".