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

Alberto Fernando Oliveira Justo1, Vitor Ribeiro Paes2, Renata Elaine Paraizo Leite2

  • 1Physiopathology in Aging Laboratory (LIM-22), University of Sao Paulo Medical School, São Paulo, São Paulo, Brazil.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging showed an association with cognitive decline, unlike Thal staging. However, this link disappeared when accounting for neurofibrillary tangle (NFT) pathology, suggesting NFTs are more critical for cognitive impairment in Alzheimer's Disease (AD).

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Alzheimer's Disease Research

Background:

  • The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Thal staging are standard methods for evaluating amyloid pathology in Alzheimer's Disease (AD).
  • Comparing these staging systems is crucial for understanding their relationship with cognitive function and tau pathology (Braak NFT staging).

Purpose of the Study:

  • To compare the effectiveness of CERAD and Thal staging in assessing amyloid pathology.
  • To evaluate the correlation of CERAD and Thal staging with cognitive outcomes and tau pathology (Braak NFT).

Main Methods:

  • Cross-sectional, population-based autopsy study using samples from the Biobank for Aging Studies.
  • Exclusion of participants with significant vascular lesions, Lewy body disease, or LATE.
  • Logistic regression analysis correlating CERAD, Thal, and Braak NFT stages with cognitive status (CDR), adjusted for covariates. Kappa statistics assessed inter-rater agreement.

Main Results:

  • Higher CERAD and Thal scores were linked to older age, female sex, lower education, and White ethnicity.
  • Individuals with frequent neuritic plaques showed worse cognition and higher Braak NFT scores.
  • CERAD scores correlated with poorer cognition (p=0.002), while Thal staging showed a borderline association (p=0.050). Braak NFT staging strongly correlated with cognitive impairment (p=0.001). After adjusting for Braak NFT, CERAD and Thal associations with cognition became non-significant.

Conclusions:

  • While CERAD scores initially appeared associated with cognition, this link was not significant after adjusting for Braak NFT staging.
  • The findings suggest that the frequency of amyloid deposits may correlate more closely with neurofibrillary tangle pathology than with Thal staging.
  • Braak NFT staging appears to be a more significant predictor of cognitive impairment in this autopsy cohort.