- TREM2 - ALZFORUM
TREM2 encodes Triggering Receptor Expressed on Myeloid Cells 2, a transmembrane receptor that modulates microglial activity and survival TREM2 variants cause Nasu-Hakola disease (NHD), a rare autosomal recessive early-onset dementia, and may modify the risk of developing Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis
- VG-3927 | ALZFORUM
In September 2023, VG-3927 became the first small-molecule TREM-2 agonist cleared to enter the clinic In October 2023, the first volunteer was treated in a Phase 1, placebo-controlled, single- and multiple-ascending-dose safety study being conducted in Miami
- All Roads Lead to TREM2: Gearing Up to Target This Receptor
Since the discovery of rare, yet potent risk variants in the TREM2 gene 11 years ago, the microglial receptor has emerged as a pivot point in the pathogenesis of Alzheimer’s disease Findings presented at the International Conference on Alzheimer’s and Parkinson’s Diseases, held March 28 to
- TREM2: A Chill Pill for Neurons? | ALZFORUM
TREM2 created quite the buzz at this year’s AD PD meeting, held April 1-5 in Vienna In the wake of a TREM2 agonist’s demise, scientists presented optimistic findings from early phase trials of a fresh batch of agonists Juxtaposing this were presentations that unveiled a new modus operandi for
- DNL919 - ALZFORUM
Background This TREM2 agonist antibody activates microglia to phagocytose amyloid DNL919 contains a transferrin-receptor binding sequence engineered into its Fc domain Thus, the antibody binds to the abundant transferrin receptors on endothelial cells of the blood-brain barrier, which facilitate its active transport into the brain
- A tetravalent TREM2 agonistic antibody reduced amyloid . . . - ALZFORUM
Zhao P, Xu Y, Jiang L, Fan X, Li L, Li X, Arase H, Zhao Y, Cao W, Zheng H, Xu H, Tong Q, Zhang N, An Z A tetravalent TREM2 agonistic antibody reduced amyloid pathology in a mouse model of Alzheimer's disease Sci Transl Med 2022 Sep 7;14 (661):eabq0095 PubMed
- Identification of senescent, TREM2-expressing microglia in . . . - ALZFORUM
This insightful paper by the Schwartz lab delves into the analysis of microglia in Alzheimer’s disease (AD) and aging models, shedding light on intriguing findings The key discovery revolves around identifying two distinct subsets of microglia within the TREM2-positive group: one associated with disease (DAM) and the other with senescence Interestingly, despite their similar
- TREM2 H157Y - ALZFORUM
The H157Y mutation reduced activation in response to phospholipid ligands in 2B4 T cells engineered to turn on GFP expression when TREM2 was engaged (Song et al , 2017) and also decreased phagocytosis of pHrodo-E Coli by HEK Flp-in cells expressing the variant (Schlepckow et al , 2017), compared with cells that expressed wild-type TREM2
|