This Northwestern Breakthroughs podcast nicely encapsulates our study. The host does a great job leading the discussion for the lay audience to digest our work. I hope this allows people to better understand the results and impact of this study. youtu.be/bZrdwGQ_Ok0

This video describes the findings from our recent study conducted at ⁦@ARC_Neuro⁩. In the video, lead author ⁦@LynnOlst⁩ and I discuss the findings and their implications for Alzheimer’s disease. youtu.be/pnRzktJRWAo

Located in vibrant downtown Chicago, our center features state-of-the-art equipment and infrastructure to make foundational discoveries in neurodegenerative disease research. Even if you are not yet finished pursuing your PhD, we want to hear from you!

The #AAIC24 opening session was quite a spectacle. The session featured a neon vapor wave-themed colonial hype band. This is a vibe that can only be experienced in Philly!

Finally, we assessed familial and sporadic AD risk genes previously identified in GWAS studies. Surprisingly, many genes associated with sporadic AD contained DARs. Many were identified in APOE 4/4 carriers. A DAR in the BIN1 gene was associated with clonally expanded T cells.

We also noted many immune cytokines contained a DAR in their promoter and were differentially expressed in an APOE-genotype-dependent manner. AD APOE4/4 carriers had several cytokine DARs in their promoters. The gene ABCA1 also stood out in APOE 4/4 carriers.

We detected CXCR3+ CD8 T cells in the AD hippocampus and meninges. The function of T cells in the AD brain is an area of investigation for many research groups. We show T cells interacting with plaque-associated microglia in the AD brain. Could they modulate microglial function?

We also assessed cis regulatory elements associated with differentially expressed genes. In CD8 T cells, we detected a cis regulatory element associated with CXCR3 expression. CXCR3 was recently shown by @mejorfi and @RudyTanzi to mediate homing of CD8 T cells to 3D AD cultures.

We next assessed genes that contained a DAR that were also differentially expressed. Here, monocytes stood out. NFKB signaling was significantly altered in these cells. We identified a unique RELA binding site in NFKB2 in AD monocytes that was adjacent to a DAR.

We first assessed differentially accessible regions (DARs) of chromatin across the major immune cell types. Notably, AD immune cells had a higher proportion of open chromatin across all cell types. Many DARs were detected in introns and promoters of genes. CD8 T cells stood out.