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Interface between tauopathies and synucleinopathies: A tale of two proteins

2006· review· en· 264 citations· W2134121616 on OpenAlex· 10.1002/ana.20819

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

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.

Candidate categories
Meta-epidemiology (narrow)
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Not applicableConsensus signal: none
Genre
Candidate signal: ReviewConsensus signal: Review
Teacher disagreement score
0.984
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.092
GPT teacher head0.386
Teacher spread
0.294 · how far apart the two teachers sit on this one work
Validation status
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

Abstract

Neurodegenerative diseases are often classified based on the abnormal accumulation of synuclein or tau. Traditionally, these disorders have been viewed as distinct clinical and pathological entities. However, advances in molecular genetics and protein biochemistry have shown intriguing overlaps. The most common synucleinopathy, Parkinson's disease, is characterized by extrapyramidal motor dysfunction, whereas the most common tauopathy, Alzheimer's disease, is defined by dementia. Yet there is overlap of clinical features; Parkinson's disease patients frequently have dementia, and Alzheimer's disease patients often manifest parkinsonism. Dementia with Lewy bodies exemplifies the existence of a continuum among these diseases. This overlap extends to the neuropathological findings; the pathognomonic hallmark for one set of disorders, Lewy bodies or neurofibrillary tangles, is present more often than expected in the other set. Moreover, mutations in LRRK2 known to cause parkinsonism are associated not only with dopaminergic neuronal degeneration, but also with the accumulation of synuclein, tau, neither, or both proteins. Other shared genetic features between tauopathies and synucleinopathies also exist. Finally, the known protein interactions between tau and synuclein further highlight the interface. Evidence for the intersection of tauopathies and synucleinopathies indicates the need for an updated disease classification scheme and may have important implications for therapeutic development.

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.

The record

Venue
Annals of Neurology
Topic
Parkinson's Disease Mechanisms and Treatments
Field
Medicine
Canadian institutions
Toronto Western Hospital
Funders
not available
Keywords
SynucleinopathiesTauopathyParkinsonismDementiaNeuroscienceDementia with Lewy bodiesParkinson's diseaseDiseaseLewy bodyAlpha-synucleinPathognomonicTau proteinBiologyMedicinePsychologyAlzheimer's diseasePathologyNeurodegeneration
Has abstract in OpenAlex
yes