Proteomic changes in Alzheimer’s disease associated with progressive Aβ plaque and tau tangle pathologies

Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer's disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest Aβ-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other…

• BF
  BrightFocus Foundation

  Award: A2021013F
• V
  Vetenskapsrådet

  Award: 2022-00775
• FD
  Fonds de Recherche du Québec - Santé

  Award: 298314