Dopaminergic Positron Emission Tomography Imaging in the Alpha‐Synuclein Preformed Fibril Model Reveals Similarities to Early Parkinson's Disease
Bibliographic record
Abstract
Abstract Background Positron emission tomography (PET) imaging in early Parkinson's disease (PD) subjects reveals that increased dopamine (DA) turnover and reduced dopamine transporter (DAT) density precede decreases in DA synthesis and storage. The rat α‐synuclein preformed fibril (α‐syn PFF) model provides a platform to investigate DA dynamics during multiple stages of α‐syn inclusion‐triggered nigrostriatal degeneration. Objectives We investigated multiple aspects of in vivo dopaminergic deficits longitudinally and similarities to human PD using translational PET imaging readouts. Methods Longitudinal imaging was performed every 2 months in PFF and control rats for 7 months. [ 18 F]‐Fluoro‐3,4‐dihydroxyphenyl‐ L ‐alanine (FDOPA) imaging was performed to investigate DA synthesis and storage (K occ ) and DA turnover, estimated by its inverse, the effective distribution volume ratio (EDVR). 11 C‐Methylphenidate (MP) was used to estimate DAT density (BP ND ). Results Early DA turnover increases and DAT binding decreases were observed in the ipsilateral striatum of PFF rats, progressing longitudinally. EDVR decreased 26%, 38%, and 47%, and BP ND decreased 36%, 50%, and 65% at the 2‐, 4‐, and 6‐month time points, respectively, compared to ipsilateral control striatum. In contrast, deficits in DA synthesis and storage were not observed in the ipsilateral striatum of PFF rats compared to control injections and were relatively preserved up to 6 months (K occ decreased 20% at 6 months). Conclusions The relative preservation of DA synthesis and storage compared to robust progressive deficits in DAT density and increases in DA turnover in the rat α‐syn PFF model display remarkable face validity to dopaminergic alterations in human PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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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 | 0.000 | 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".