Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers.

Original languageEnglish (US)
Article number4001
Pages (from-to)4001
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - Jun 28 2021

Keywords

  • Aged
  • Alzheimer Disease/cerebrospinal fluid
  • Amyloid beta-Peptides/cerebrospinal fluid
  • Biomarkers/cerebrospinal fluid
  • Cerebrospinal Fluid Proteins/analysis
  • Cognitive Dysfunction/pathology
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins/cerebrospinal fluid
  • Peptide Fragments/cerebrospinal fluid
  • Prognosis
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor, Type I/cerebrospinal fluid
  • tau Proteins/cerebrospinal fluid

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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