ArticleBrain : a journal of neurology2026
Estimating the time course of biomarker changes in Alzheimer's disease.
Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Exploring the neuropathological basis of lateral ventricular enlargement in elderly patients with schizophrenia.Psychiatry and clinical neurosciences · 2026Article
- Exploring the Gut-Brain Connection: Are Probiotics the Next Frontier in Alzheimer's Disease Treatment?Probiotics and antimicrobial proteins · 2026Review
- Early Alzheimer´s disease blood biomarkers are associated with a higher risk for postoperative long-term cognitive decline: Insights from the FINDERI study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- What Does a Positive Alzheimer Disease Blood-Based Biomarker Result Mean in People With Mild Cognitive Impairment?Neurology · 2026Review
- Willingness and barriers to blood-based biomarker testing of Alzheimer's disease in the general population in the Czech Republic.Alzheimer's research & therapy · 2026Article
- Characterisation of patients with intracerebral haemorrhage with mixed location haemorrhages: clinical and imaging features, CSF neurodegeneration markers and recurrence risk.European stroke journal · 2026Article
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- Prospective study on clinical utility of plasma p-Tau217 and other biomarkers in Japanese memory clinics using the LUMIPULSE platform.Alzheimer's research & therapy · 2026Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Recent advancements in biomarkers have transformed Alzheimer's disease (AD) diagnosis from being purely symptom-based to include biological criteria. With new treatments targeting the core biology of Alzheimer's disease, understanding the timeline of biological changes is crucial as the disease progresses over decades. Longitudinal data from amyloid-beta (Aβ) PET and cognitive tests [Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog)] from the Alzheimer's Disease Neuroimaging Initiative (n = 1448) and BioFINDER (n = 2088) were used to stage patients against an estimated continuous disease timeline (predicted time since Aβ-PET positivity). The estimated timeline was validated by comparing correlations with unseen biomarkers and cognitive measures against alternative staging approaches. Trajectories for plasma, CSF, MRI and PET biomarkers, measuring Aβ, tau and neurodegeneration, were mapped along this Alzheimer's disease continuum. The proposed staging approach was found to produce stronger correlations with unseen cognitive measures and biomarkers compared to alternative staging methods, including amyloid and tau PET clocks (all pairwise P < 0.05). Findings related to biomarker trajectories were highly consistent across cohorts. The period from Aβ-PET positivity to end-stage Alzheimer's disease dementia (MMSE = 0) was estimated at 20-25 years, with a presymptomatic phase of 7-11 years. CSF Aβ42/Aβ40 became abnormal about a year before Aβ-PET positivity, CSF phosphorylated-tau (p-tau)231, p-tau217 and plasma phosphorylated/neuritic plaque-tau217 1-3 years after, and tau-PET about 8 years after. Neurodegenerative biomarkers, such as hippocampal volume, became clearly abnormal in early dementia stages, 14-16 years after Aβ-PET positivity. The progression from initial biomarker abnormality to severe Alzheimer's disease spans two decades. Disease progression modelling elucidates the evolution of AD biomarkers and cognition, highlighting the relative timing of biomarker abnormalities. These models can determine disease stages, aiding in prognosis and the evaluation of disease-modifying treatments.
Indexed as
Identifiers
What OpenQuestion holds
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.