Dlgap2: The Gene Associated With Memory Loss

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A recent study¹ led by The Jackson Laboratory and University of Maine has discovered that the gene Dlgap2 is associated with Alzheimer disease, dementia, and cognitive decline. Researchers found post-mortem human brain tissues of individuals experiencing “poorer cognitive health” and “faster cognitive decline” had low levels of Dlgap2.

“The reason why this is so important is because a lot of research around cognitive aging and Alzheimer’s has been hyper-focused on well-known risk genes like APOE and brain pathologies,” Catherine Kaczorowski, associate professor and Evnin family chair in Alzheimer disease research at The Jackson Laboratory (JAX), and adjunct professor with the University of Maine Graduate School of Biomedical Science and Engineering (GSBSE), said to the press. “We wanted to give ourselves the option of looking at new things people keep ignoring because they've never heard about a gene before.”²

Located in the synapses of neurons, Dlgap2 anchors critical receptors for signals between learning and memory neurons. The research team examined the memory and brain tissue from a large group of genetically diverse mice, relying on diversity outbred mice. The population came from 8 parents created by JAX, as they thought a diversified group would better reflect genetic diversity in humans. About 437 mice, each either 6, 12, or 18 months old were used.

“It’s great because you can harness the best parts of a mouse study and human society,” Andrew Ouellette, a PhD student at JAX and a GSBSE NIH T32 predoctoral awardee, said to the press. “Historically, research has been done with inbred mice with similar genetic makeups; same, similar genetic models. But clinically, humans don't work like that because they're not genetically identical.”²

Quantitative trait loci mapping was performed on the mouse population. Study of entire genome sequences allowed for identification of the genes responsible for varying cognitive function and where they occurred. Researchers pinpointed the connection between Dlgap2 and memory decline in mice, and were then able to evaluate its significance to humans.

They found Dlgap2 is associated with the degree of memory loss in mice and risk for Alzheimer dementia in humans. Further research will be needed to determine how the gene influences dementia and brain functioning.

References

1. Ouellette AR, Neuner SM, Dumitrescu L, Hadad N, et al. Cross-species analyses identify Dlgap2 as a regulator of age-related cognitive decline and alzheimer’s dementia. Cell Reports. 2020;32(9):108091.

2. University of Maine. New connection between Alzheimer's dementia and Dlgap2. News release. ScienceDaily. November 23, 2020. https://www.sciencedaily.com/releases/2020/11/201123161040.htm