60 RESULTS
COMMENT This work provides compelling evidence that CD8+ T cells and microglia interactions are pivotal in the myelin pathology observed in Alzheimer’s disease (AD). Using the 5xFAD mouse model, the authors demonstrated that CD8+ T cells trigger microglial activa
COMMENT In recent decades, substantial strides have been made in unraveling the genetic factors and biological mechanisms underlying Alzheimer’s disease, with a primary focus on microglia as the brain's resident immune cells. However, it is now widely recogn
COMMENT As a note of historical clarification, while not mentioned in this article, the first second-generation, non-NSAID, GSMs were discovered by Steve Wagner and me in 2002 at Neurogenetics, Inc., later TorreyPines Therapeutics, Inc. Our original GSM program w
COMMENT This organoid system described by Gage and colleagues is a big step forward in attempts to model AD with human cells. It will now be critical to determine whether these microglia, matured in transplanted human brain organoids, would more closely mimic dis
COMMENT In this study, Levine et al. utilize the FinnGen and U.K. Biobank to examine associations between neurodegenerative diseases (NDDs) and viral infections. Using the recent discovery of Epstein-Bar virus’ association with multiple sclerosis as a positive co
COMMENT Using multiple whole-exome sequencing (WES) datasets on early and late-onset Alzheimer’s disease patients and controls from several consortia, Holstege and colleagues assessed the burden of predicted, rare, damaging variants in exomes from roughly 32,000
COMMENT Wang et al. elegantly described new mechanistic insights into how TREM2 induces microglial cell responses to Aβ in mouse models of Alzheimer’s disease (AD) through SYK-dependent and SYK-independent pathways. Recent studies have shown characteristic expres
COMMENT We are pleased to see the AD genetics field rapidly expanding beyond traditional GWAS—which reveal common variants with highly significant genetic association with AD, but with usually no effects on gene function or AD pathobiology—to the identification o
COMMENT Steve Wagner was one of my very best friends and closest collaborators for the past 35 years. I remember first meeting Steve in Maratea, Italy, and then 10 years later, that beautiful sunny day in 1998 when we were walking along Nantasket beach, just sout
COMMENT So much has been said about the monumental contributions to AD and FTLD research by John—still, we would need thousands more commentaries to cover it all. I remember John as a warm, incredibly compassionate and fun human being. I would have to say that am
COMMENT We agree that γ-secretase modulators (GSMs) are an excellent alternative for regulating Aβ levels in a hopefully safer manner than what has been experienced with γ-secretase and β-secretase inhibitors. My close colleague Steve Wagner and I have been devel
COMMENT This is a carefully prepared study of a homogenous cohort of Ashkenazi Jewish centenarians and controls from the same households. The authors used whole-exome sequencing to study rare variant associations (and enrichment) with longevity. While single vari
COMMENT The new data from the Cruchaga lab are very intriguing and shine a particular spotlight on the role of CD33 in AD pathogenesis. We first described the genetic association of CD33 with AD risk in a family-based GWAS in 2008 (Bertram et al., 2008) and later
COMMENT In this interesting new study, Lopatko Lindman et al. examined the impact of antiviral treatment on long-term risk of dementia in a large Swedish registry-based cohort, focusing on herpes simplex virus (HSV) and varicella zoster virus (VZV), two highly pe
COMMENT Emerging evidence strongly supports that neural-glial interactions play a pivotal role in Alzheimer's disease pathogenesis. However, there are few human cellular models for studying these interactions. Lorenz Struder's team described a fully def
