Microglia as dynamic and essential components of the amyloid hypothesis

Abstract

In this issue, Griciuc et al investigate the Alzheimer’s disease risk gene, CD33. AD brains have increased CD33 and CD33-positive microglia. Mice lacking CD33 have less AD pathology suggesting a role of microglia for Aβ clearance and development of future therapies.

Figure 1

A Subnetwork of Complement System Molecules from a Bayesian Brain Immune and Microglia Module Contains CD33 and TYROBP. This module correlates with multiple late-onset AD clinical covariates and is enriched for immune functions and pathways related to microglia activity. The complement network is derived from multiscale analysis of genetic linkage information and AD brain gene expression information. The subnetwork shown here is derived from a subgroup of genes related to complement. MHC, Fc, cytokine, and toll-like receptor networks are also part of the module but are not shown. Core family members are shaded darkly, whereas square nodes denote literature-supported nodes (at least two PubMed abstracts implicating the gene or final protein complex in LOAD or a model of LOAD). Labeled nodes are either highly connected in the original network, literature-implicated LOAD genes, or core members of one of the five immune families. Node size is proportional to connectivity in the module (from Zhang et al., 2013, with permission).