CNCM Newsletter #2

UCI Center for Neural Circuit Mapping

We’re thrilled to announce the release of our newest newsletter! This edition acknowledges our members’ achievements and highlights what to look forward to this year and beyond. Inside, you’ll find a closer look at our Viral Core updates, upcoming conference and seminar announcements, and more. Dive in to discover what we’ve been up to and how you can get involved!

The full newsletter can be read here.

UC Irvine-led team reveals how TREM2 genetic mutation affects late-onset Alzheimer’s

Irvine, Calif., Aug. 6, 2024 — Researchers led by the University of California, Irvine have discovered how the TREM2 R47H genetic mutation causes certain brain areas to develop abnormal protein clumps, called beta-amyloid plaques, associated with late-onset Alzheimer’s disease. Leveraging single-cell Merfish spatial transcriptomics technology, the team was able to profile the effects of the mutation across multiple cortical and subcortical brain regions, offering first-of-their-kind insights at the single-cell level.

The study, recently published online in the journal Molecular Psychiatry, compared the brains of normal mice and special mouse models that undergo changes like those in humans with Alzheimer’s.

Findings revealed that the TREM2 mutation led to divergent patterns of beta-amyloid plaque accumulation in various parts of the brain involved in higher-level functions such as memory, reasoning and speech. It also affected certain cell types and their gene expression near the plaques.

“Alzheimer’s disease progresses differently in individuals with various genetic risk factors,” said principal investigator Xiangmin Xu, UC Irvine Chancellor’s Professor of anatomy and neurobiology and director of the campus’s Center for Neural Circuit Mapping. “By profiling known mutations, we can develop early, personalized treatments before cognitive decline begins.”

Team members analyzed 19 sections of mouse brains and more than 400,000 cells using a special technique called Merfish to see how they were affected by the Alzheimer’s-related mutations. They were able to examine the expression patterns of genes, providing insight into how they are regulated, contribute to cellular functions and respond to stimuli. Their analysis showed that disparate mutations, like TREM2 R47H, cause changes in the ways microglia and astrocyte cells react to inflammation, as well as how neurons communicate and support brain health.

“Early intervention is key to preventing severe cognitive decline. This is the first study to look at the entire brain at such a detailed level, enabling us to gain a deeper understanding of how the TREM2 R47H mutation impacts gene expression in specific cell types,” Xu said. “These insights can help develop targeted therapies that address these changes and can lead to early intervention strategies that help prevent or slow down the progression of Alzheimer’s disease.”

Read the full article here