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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Alexa Pichet Binette1,2,3, Ruben Smith4,5, Gemma Salvadó1,6

  • 1Clinical Memory Research Unit, Lund University, Lund, Sweden.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

New Alzheimer's disease (AD) criteria using tau-PET show that co-pathologies significantly influence symptom severity. Understanding these discrepancies is key for accurate AD diagnosis and prognosis.

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Area of Science:

  • Neurology
  • Biomarker Research
  • Neurodegenerative Diseases

Background:

  • The latest Alzheimer's disease (AD) criteria integrate tau-PET imaging as a core biomarker.
  • The spatial extent of tau pathology is now part of the revised biological staging for AD.
  • This study aimed to implement and validate these new criteria in a large cohort.

Purpose of the Study:

  • To implement updated Alzheimer's disease (AD) staging criteria incorporating tau-PET in a large research cohort.
  • To compare individuals with congruent biological and clinical stages versus those with discrepant stages.
  • To investigate the role of co-pathologies and demographics in individuals with mismatched AD stages.

Main Methods:

  • 838 amyloid-beta-positive participants from the BioFINDER-2 cohort with tau-PET ([18F]RO948) data were analyzed.
  • Participants were classified based on both clinical staging (cognitively normal to dementia) and biological staging (early to advanced).
  • Demographics, neurodegeneration markers (cortical thickness, TDP-43 MRI signature, NfL), alpha-synuclein, GFAP, and cerebrovascular lesions were compared between congruent and discrepant staging groups.

Main Results:

  • 51.3% of participants showed more advanced clinical impairment than biological stage (Clinical > Biological).
  • The Clinical > Biological group was older, had more men, higher alpha-synuclein, elevated NfL, greater TDP-43 atrophy, and more small vessel disease.
  • Individuals with more advanced biological stage than clinical (Biological > Clinical) had less neurodegeneration (thicker cortex).

Conclusions:

  • The study validates the new AD staging criteria, emphasizing the role of co-pathologies in symptom severity.
  • Individuals with less tau pathology than expected for their clinical stage often exhibit significant co-pathologies.
  • Measuring non-AD biomarkers is crucial for patients with cognitive impairment disproportionate to their biological AD stage, impacting diagnosis and prognosis.