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Record W4311504638 · doi:10.1002/acn3.51695

Plasma phosphorylated tau181 predicts cognitive and functional decline

2022· article· en· W4311504638 on OpenAlexfundno aff
Thomas F. Tropea, Teresa Waligórska, Sharon X. Xie, Ilya M. Nasrallah, Katheryn A Q Cousins, John Q. Trojanowski, Murray Grossman, David J. Irwin, Daniel Weintraub, Edward B. Lee, David A. Wolk, Alice Chen‐Plotkin, Leslie M. Shaw

Bibliographic record

VenueAnnals of Clinical and Translational Neurology · 2022
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersNorman Cousins Center for PsychoneuroimmunologyNational Institute of Neurological Disorders and StrokeNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthH. Lundbeck A/SEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaTakeda Pharmaceuticals U.S.A.GE HealthcareAlzheimer's Disease Neuroimaging InitiativeF. Hoffmann-La RocheUniversity of PennsylvaniaAbbVieRocheUniversity of Southern CaliforniaChan Zuckerberg InitiativeNovartis Pharmaceuticals CorporationEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Drug Discovery FoundationMerckAlzheimer's AssociationAmerican Heart AssociationFoundation for the National Institutes of Health
KeywordsMedicinePhosphorylationCognitionCognitive declineInternal medicineCell biologyPsychiatryDiseaseDementia

Abstract

fetched live from OpenAlex

OBJECTIVE: To determine if plasma tau phosphorylated at threonine 181 (p-tau181) distinguishes pathology-confirmed Alzheimer's disease (AD) from normal cognition (NC) adults, to test if p-tau181 predicts cognitive and functional decline, and to validate findings in an external cohort. METHODS: Thirty-one neuropathology-confirmed AD cases, participants with clinical diagnoses of mild cognitive impairment (MCI, N = 91) or AD dementia (N = 64), and NC (N = 241) had plasma collected at study entry. The clinical diagnosis groups had annual cognitive (Mini-Mental State Examination, MMSE) and functional (Clinical Dementia Rating Scale, CDR) measures. NC (N = 70), MCI (N = 75), and AD dementia (N = 50) cases from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used as a validation cohort. Plasma p-tau181 was measured using the Quanterix SiMoA HD-X platform. RESULTS: Plasma p-tau181 differentiated pathology-confirmed AD from NC with negative amyloid PET scans with an AUC of 0.93. A cut point of 3.44 pg/mL (maximum Youden Index) had a sensitivity of 0.77, specificity of 0.96. p-Tau181 values above the cut point were associated with the faster rate of decline in MMSE in AD dementia and MCI and a shorter time to a clinically significant functional decline in all groups. In a subset of MCI cases from ADNI, p-tau181 values above the cut point associated with faster rate of decline in MMSE, and a shorter time to a clinically significant functional decline and conversion to dementia. INTERPRETATION: Plasma p-tau181 differentiates AD pathology cases from NC with high accuracy. Higher levels of plasma p-tau181 are associated with faster cognitive and functional decline.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.115
GPT teacher head0.405
Teacher spread0.291 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations33
Published2022
Admission routes1
Has abstractyes

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