A matrisomal proteomics network modulates tau and amyloid‐beta toxicity in fly AD models.

Mounting evidence indicates Alzheimer’s disease (AD) has a complex etiology where insults in multiple pathways conspire to disrupt neuronal function, yet the molecular changes underlying AD remain poorly understood. To identify protein changes associated with AD, we previously performed mass‐spectrometry on post‐mortem brain tissue from longitudinal cohorts and identified >40 protein coexpression networks correlated to AD pathological and clinical traits. A small module (M42) consisting of 37 proteins linked to the extracellular matrix (ECM/matrisome) has the strongest correlation to AD pathology (r=0.75), and includes several proteins linked to AD (e.g. APP, APOE) including SMOC1 as the central hub. SMOC1 has conserved roles in modulating TGF‐Beta and wnt signaling during development, however, its role in the adult brain remains unstudied.