Lack of central and peripheral nervous system synuclein pathology in R1441G<i>LRRK2</i>-associated Parkinson’s disease
Bibliographic record
Abstract
In idiopathic Parkinson’s disease (iPD) abundant alpha-synuclein (αSyn) aggregates are present in the central and peripheral autonomic nervous system (PANS). Detection of αSyn aggregates in the peripheral tissue has been suggested as a potential diagnostic marker of Parkinson’s disease (PD) in early and premotor stages.1 The neuropathology of LRRK2 -associated PD ( LRRK2 -PD) is unexpectedly heterogeneous.2 In most G2019S mutation carriers αSyn loaded Lewy bodies and neurites can be found in the central nervous system (CNS). Some cases though lack the Lewy-type pathology and may show non-specific nigral degeneration. Prominent tau pathology can also be found. Information on neuropathological findings in cases of PD associated with other LRRK2 mutations is very limited, and we are not aware of reports describing the involvement of the PANS. Here we describe postmortem central and peripheral neuropathological findings in a PD patient carrier of the R1441G mutation in the LRRK2 gene. A 67-year-old man presented with gait instability and clumsiness in the right leg. At neurological examination, he had hypomimia, action tremor in the right hand, mild asymmetric bradykinesia and rigidity. He suffered from alcohol-related liver disease, diabetes mellitus and polyneuropathy. He had no hyposmia, depression, constipation, orthostatic hypotension, and urinary or erectile dysfunction. Levodopa was started with a good response. His daughter was diagnosed with PD at the age of 32. Genetic analysis revealed a heterozygous R1441G LRRK2 mutation in both of them. Over the following years the disease progressed slightly. At the age of 69 the …
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".