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1H-MR spectroscopy biomarkers are associated with plasma-derived biomarkers of amyloid-β and tau in the early phase of AD continuum

2025· article· en· W4416095575 on OpenAlexfundno aff
Firat Kara, James M. Joers, Scott A. Przybelski, Alicia Algeciras-Schimnich, Jeffrey L. Gunter, Clifford R. Jack, Ronald C. Petersen, Gülin Öz, Kejal Kantarci

Bibliographic record

VenueNeurobiology of Aging · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingPharmaceuticals BayerLife Sciences, University of California, Los AngelesMayo ClinicEisai CanadaBayer ScheringNational Cancer InstituteNational Institutes of HealthNational Institute of Biomedical Imaging and BioengineeringAlzheimer's Drug Discovery Foundation
KeywordsGliosisBiomarkerPosterior cingulateCreatineHippocampusCognitionCognitive impairment

Abstract

fetched live from OpenAlex

The objective of the study was to evaluate the relationship of plasma biomarkers of Alzheimer's disease (AD) with in vivo proton magnetic resonance spectroscopy (¹H-MRS) markers, and their association with cognitive function across the early stages of the AD continuum. Determining these associations may clarify the AD-related biological pathways and support the development of integrated AD blood and ¹H-MRS biomarkers for early detection of these pathways. Fifty-five older adults (40 cognitively unimpaired; 15 mild cognitive impairment) from the Mayo Clinic Study of Aging underwent single-voxel ¹H-MRS (sLASER) at 3T in the posterior cingulate gyrus (PCG) and left hippocampus (LH), along with plasma assays for Aβ42/40, phosphorylated tau (p-tau181), and the p-tau181/Aβ42 ratio. Associations between plasma biomarkers and ¹H-MRS metabolites (myo-inositol [mIns]/total creatine [tCr], total N-acetylaspartate [tNAA]/tCr, and tNAA/mIns) were examined using partial Spearman correlations (rho, ρ) adjusted for age and sex. Next, associations of the Mini-Mental State Examination with p-tau181/Aβ42 and tNAA/mIns were examined adjusting for the same covariates plus education. In both PCG and LH regions, lower tNAA/mIns was associated with higher p-tau181/Aβ42 (PCG:ρ=-0.59; LH:ρ=-0.54) and p-tau181 (PCG: ρ=-0.38; LH:ρ =-0.39), as well as with lower Aβ42/40 (PCG:ρ=0.40; LH:ρ=0.32). Higher mIns/tCr was associated with higher p-tau181/Aβ42 (PCG: ρ=0.56; LH:ρ=0.46) and p-tau181 (PCG:ρ=0.37; LH:ρ=0.31). Lower PCG and LH tNAA/mIns ratios were associated with lower MMSE (PCG:ρ=0.53; LH:ρ=0.46), while higher p-tau181/Aβ42 was associated with lower MMSE (ρ=-0.49). ¹H-MRS-derived gliosis and neuronal injury biomarkers are associated with early AD pathology, and cognitive performance, supporting their use as noninvasive biomarkers in early AD.

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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.014
GPT teacher head0.304
Teacher spread0.290 · 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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Citations2
Published2025
Admission routes1
Has abstractno

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