Evidence map›Paper›PMID 41225647›Full record

Observational studyAlzheimer's research & therapy2025

Prognostic value of plasma biomarkers in early Alzheimer's disease: a longitudinal clinical and neuroimaging study.

Frederikke Kragh Clemmensen, Mathias Holsey Gramkow, Fernando Gonzalez-Ortiz, Andréa Lessa Benedet, Kübra Tan, Wiebke Traichel, Ulrich Lindberg, Otto Mølby Henriksen, Henrik Zetterberg, Kaj Blennow and 4 more

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05175664 (TRacking Alzheimer´s Disease), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05175664 completednot on this map

TRacking Alzheimer´s Disease: a Study of Disease trajeCtory and Development of Diagnostic and Disease Stage biomarKers in AD (TRACK-AD)

TypeobservationalSponsorDanish Dementia Research CentreRan2022 to 2024Enrolled350ConditionsAlzheimer Disease, Mild Cognitive Impairment, Neuro-Degenerative Diseases, Vascular DementiaArmsLong-term study, Short-term study, Cross-sectional study
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Frederikke Kragh ClemmensenDanish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital-, Rigshospitalet, Inge Lehmans Vej 8, Copenhagen, 2100, Denmark. frederikke.kragh.clemmensen@regionh.dk.
Mathias Holsey GramkowDanish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital-, Rigshospitalet, Inge Lehmans Vej 8, Copenhagen, 2100, Denmark.
Fernando Gonzalez-OrtizDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Andréa Lessa BenedetDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kübra TanDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Wiebke TraichelDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Ulrich LindbergDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Otto Mølby HenriksenDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Ian LawDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Anja Hviid SimonsenDanish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital-, Rigshospitalet, Inge Lehmans Vej 8, Copenhagen, 2100, Denmark.
Kristian Steen FrederiksenDanish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital-, Rigshospitalet, Inge Lehmans Vej 8, Copenhagen, 2100, Denmark.
Steen Gregers HasselbalchDanish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital-, Rigshospitalet, Inge Lehmans Vej 8, Copenhagen, 2100, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhile blood biomarkers for AD have proven useful in identifying AD pathology from other neurodegenerative conditions, their prognostic value in real-world clinical settings, such as memory clinics, remains unexplored. We aimed to examine the prognostic value of AD plasma biomarkers and their short-term changes within 4 months, for predicting clinical and neuroradiological progression over two years.

methodWe performed a prospective observational longitudinal cohort study of patients with early stages of AD and followed them for up to 2 years. Plasma was analysed for neurofilament light (NfL), brain-derived tau (BD-tau), phosphorylated tau 217 (p-tau217), and glial fibrillary acidic protein (GFAP) on single molecule array. The outcomes were annual changes in clinical dementia rating scale, sum of boxes (CDR-SB) and changes in [18F]-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI) brain scans. We performed linear regression models with baseline and short-term plasma biomarker changes as predictors, adjusted for age, sex, and creatinine.

resultsIn total, 94 patients with MCI or dementia due to AD had baseline and one-year follow-up, with 85 patients completing two-year follow-up. We found that baseline plasma NfL was significantly associated with an increase in CDR-SB at one- and two-year follow-up. Neither plasma BD-tau, p-tau217 or GFAP were associated with future clinical progression. Short-term changes of plasma NfL were associated with reduced glucose metabolism in the hippocampus and temporal cortex on [18F]FDG-PET. Short-term changes in plasma p-tau217 were significantly associated with reduced hippocampal glucose metabolism, and further, short-term changes in the p-tau217/BD-tau ratio were significantly associated with reduced metabolism in hippocampal and isthmus cingulate cortex on [18F]FDG-PET. We found no association between plasma biomarkers and MRI volumetric changes after multiple testing correction.

conclusionOur findings indicate that plasma NfL can serve as a predictor for subsequent clinical progression in early AD. Short-term changes in AD-related plasma biomarkers may reflect underlying disease processes, however, several limitations affect their interpretability. Therefore, short-term changes should be evaluated carefully and always in the context of baseline levels and clinical characteristics.

trial registrationClinicaltrials.gov (NCT05175664), date of registration 2021–12-01.

Indexed as

Alzheimer DiseaseBrainGlial Fibrillary Acidic ProteinNeurofilament Proteinstau ProteinsAgedBiomarkersDisease ProgressionFemaleFluorodeoxyglucose F18HumansLongitudinal StudiesMagnetic Resonance ImagingMalePhosphoproteinsPositron-Emission TomographyBiomarkersFluorodeoxyglucose F18GFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPhosphoproteinspTau217tau ProteinsAlzheimer’s diseaseBlood biomarkersDementiaDisease progressionMemory clinicNeurodegenerationPrognosisVariability

Identifiers

PMID41225647
PMCPMC12613411

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.