A Meta-Analysis of α-Synuclein Multiplication in Familial Parkinsonism
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Chronic alpha-synuclein (SNCA) overexpression is a relatively homogenous and well defined cause of parkinsonism and dementia. Parkinson’s disease (PD), PD with dementia, dementia with Lewy bodies and multiple system atrophy all manifest in SNCA multiplication families. Herein we summarize genealogic, clinical and genetic data from 59 families (25 not previously published) with parkinsonism caused by SNCA multiplications. Longitudinal clinical assessments and genealogic relationships were documented for all family members. All probands were genotyped with an Illumina MEGA high-density genotyping array to identify copy number variants (CNV) and enable SNCA multiplication breakpoints to be defined. Three SNCA short tandem repeat (STR) markers were genotyped in all available samples to validate genomic dosage and inheritance. A web-application was built as a forum for future data sharing. CNV analysis identified 49 subjects with heterozygous SNCA duplication (CNV3), 2 with homozygous duplication (CNV4) and 7 with a triplication mutation (CNV4). Clinical presentations varied greatly throughout the cohort. SNCA dosage correlates with disease onset (mean age of onset CNV3: 46.9±10.5 years vs. 34.5±7.4 CNV4, p=0.003). Atypical or more severe clinical courses were described in several patients and dementia was noted in 50.9% of the probands. Neither the multiplication size (average 2.05±2.45Mb) nor the number of genes included (range 1 to 50) was associated with motor symptom onset or dementia. Families with SNCA multiplication are rare and globally-distributed. Nevertheless, they may both inform and benefit from the development of SNCA targeted therapeutic strategies relevant to the treatment of all alpha-synucleinopathies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 it