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Alzheimer's Imaging Consortium.

Ilaria Pola1, Nicholas J Ashton2,3,4,5,6, Marco Antônio De Bastiani7

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This study identifies key inflammatory proteins in Alzheimer's disease (AD) linked to amyloid-beta (Aβ) and tau pathology. These findings offer potential biomarkers for tracking neuroinflammation and disease progression in AD.

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Area of Science:

  • Neuroscience
  • Immunology
  • Biomarker Discovery

Background:

  • Neuroinflammation is increasingly recognized as a critical factor in Alzheimer's disease (AD) pathogenesis.
  • Identifying reliable biomarkers for brain inflammation in AD is challenging due to complex immune responses and CNS-peripheral interactions.
  • This study investigates immune-related proteins in cerebrospinal fluid (CSF) and plasma concerning amyloid-beta (Aβ) and tau positron emission tomography (PET) imaging.

Purpose of the Study:

  • To characterize immune-related proteins in CSF and plasma in relation to Aβ and tau PET.
  • To identify potential biomarkers reflecting neuroinflammation in the AD continuum.
  • To explore the dynamic changes of these proteins during disease progression.

Main Methods:

  • Analysis of 309 inflammation-related proteins in CSF and plasma from the Translational Biomarker for Aging and Dementia (TRIAD) cohort using NULISA technology.
  • Utilized Aβ PET ([18F]AZD4694) and tau PET ([18F]MK6240) imaging data.
  • Validation performed in independent cohorts (ADNI for CSF, BBDP for plasma) using SomaScan and NULISA technologies, respectively. Linear models assessed protein associations with PET SUVR, controlling for age and sex.

Main Results:

  • Several proteins showed distinct associations with Aβ and tau pathologies, with some correlating specifically with Aβ-PET or tau-PET levels.
  • Findings were validated in independent cohorts, confirming the robustness of identified protein patterns.
  • Analysis revealed proteins that change along a disease pseudo-time, indicating their potential role in Alzheimer's disease progression.

Conclusions:

  • This preliminary multi-omics study provides novel insights into inflammatory proteins and pathways associated with Aβ and tau accumulation in Alzheimer's disease.
  • Identified proteins and pathways may serve as potential biomarkers for neuroinflammation across the AD continuum.
  • Further expansion and detailed analysis in additional cohorts are planned to solidify these findings.