September 3, 2020

New clue to Alzheimer’s disease

Combining studies of genetically diverse mouse populations and human data led to the identification of a gene associated with cognitive decline and brain changes in Alzheimer’s disease.

Reduced expression of Dlgap2, a gene important in signaling across the synapse between nerve cells, is associated with faster cognitive decline in patients with Alzheimer’s disease and increased plaques and tangles found in their brains on autopsy. 

To better understand the role of Dlgap2 in Alzheimer’s disease, Timothy Hohman, PhD, and colleagues combined their analysis of human data with studies of the Diversity Outbred mouse population conducted by a multidisciplinary group at the Jackson Laboratory in Bar Harbor, Maine, and elsewhere led by Catherine Kaczorowski, PhD.  

The collaboration, detailed in the journal Cell Reports, led to the discovery of a novel neuroprotective role for Dlgap2. Among other findings, mutant mice lacking the gene had a reduced density of dendritic spines (part of the synapse) and deficits in synaptic communication. 

These findings highlight the benefit of using genetically diverse mouse populations and the power of interdisciplinary collaborations to reveal molecular mechanisms and identify novel therapeutic targets in complex human diseases.

This research was supported in part by National Institutes of Health grants AG049164 and AG059716.