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Record W3030476832 · doi:10.1038/s41467-020-15701-2

Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease

2020· article· en· W3030476832 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsSunnybrook Health Science CentreSt Joseph's Health CentreMcGill UniversitySt Joseph's Health CareMontreal Neurological Institute and Hospital
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchParkinsonfondenNational Institutes of HealthLudmer Centre for Neuroinformatics and Mental HealthIXICOH. Lundbeck A/SGenentechMarcus och Amalia Wallenbergs minnesfondKnut och Alice Wallenbergs StiftelseServierSkånes universitetssjukhusVetenskapsrådetEisaiLunds UniversitetGovernment of CanadaNorthern California Institute for Research and EducationPfizerBiogenBioClinicaAustralian GovernmentF. Hoffmann-La RocheUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationAlzheimer's Disease Neuroimaging InitiativeEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAvid RadiopharmaceuticalsParkinson Research FoundationBristol-Myers SquibbAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsTau pathologyNeuroscienceTau proteinAlzheimer's diseaseHuman brainDiseasePathologicalBiologyPsychologyMedicinePathology

Abstract

fetched live from OpenAlex

Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.383
Threshold uncertainty score0.656

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.119
GPT teacher head0.403
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it