Fig. 1.

Alpha2 macroglobulin (A2M) is a sex-specific marker of neuronal injury in preclinical Alzheimer's disease (AD. A: using the BIOCARD and ADNI studies, we explored associations between A2M and cerebrospinal fluid (CSF) measures of preclinical AD pathophysiology and risk of mild cognitive impairment (MCI)/AD. B: using publicly available gene expression data acquired from the GTEx project (https://www.gtexportal.org/home/), we tested the association between blood and brain A2M gene expression. C: using publicly available gene expression data acquired from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/), we explored global gene networks driving A2M gene expression (C.I.) and brain-specific gene expression correlations (C.II.). Protein expression data from autopsy samples in the Baltimore Longitudinal Study of Aging (BLSA) was used to validate gene expression findings (C.III.). [Reproduced from Varma et al. (65) with permission.]