Single-nucleus transcriptomics of postmortem AD brain and mouse models of amyloidosis hammers home the species-specific responses of microglia to Aβ pathology.
Three studies found no link between vascular disease and cerebral amyloidosis.
Positive allosteric modulators improve learning and memory in mouse models of AD and epilepsy.
In Alzheimer’s brain, granulovacuolar bodies in neurons harbor activated necrosomes. They correlate with tau pathology and neuron loss, raising new questions about how neurons die in this disease.
The cells are primed to attack. Their targets include Epstein-Barr virus peptides.
In early Alzheimer’s disease, the pattern of tau deposition also strongly predicts areas destined for subsequent degeneration.
Besides further broadening the Alzheimer’s therapeutic pipeline, researchers urge a return to Phase 2, using artificial intelligence tools to streamline aspects of trials.
Data from different next-generation tracers look similar. It shows spreading plaques kick off tangles by Braak region; memory starts slipping later.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Dash Genomics, Inc., Abcam, BrainXell, and the Jackson Laboratory.
Monstrous story alert! The year 2019 was a bumper one for AD research, from single-cell transcriptomics to clinical trials, and summarizing the highlights took a lot of ink. Brace yourself, aficionados. Our Year in Research story may seem like “The Neverending Story,” but at least it’s not fantasy! As usual, we divvied things up into bite-size pieces to read one at a time in case it’s just too much in one gulp. Or consider printing the opus grande, and reserving some quality time on your favorite lounge chair.
A new single-nucleus transcriptomic analysis confirms that microglial responses to amyloid vary by species. In mice, the cells dial down homeostatic genes and boost a disease-associated microglial signature, aka DAM. In AD brain, microglia turn up homeostatic genes and other AD genes such as SORL1. In both cases, however, mutation or loss of TREM2 weakens the microglial response, highlighting the critical role of this receptor.
Gangs of cytotoxic CD8+ T cells were found roving the cerebrospinal fluid and brains of people with Alzheimer’s and Parkinson’s disease. The cells appeared to be doing more than merely passing through. They had multiplied, which is evidence that they were responding to specific antigens. The identity of most of those antigens remains a mystery, but some T cells recognized Epstein-Barr virus peptides.
Researchers are grappling with how to interpret tau PET, and CTAD added grist for the mill. In one surprise, tau PET scans with PI-2620 can turn positive in some people with prodromal AD even before global amyloid does. However, tangle burden varies widely, with some people maintaining pristine tau scans even at high amyloid loads. Much of the timing of when a person is considered globally positive for amyloid or tau PET depends on how cutoffs are set, and the definition of prodromal AD may shift with the increasing use of more sensitive cognitive tests. Meanwhile, though, longitudinal data shows that baseline tracer uptake predicts future cognitive decline, which may help researchers select patients for clinical trials based on a tau cutoff.
Polish your abstract for the 3rd Kolster Seeon meeting, organized by Stefan Lichtenthaler, Technical University of Munich. To be held June 8-10, 2020 in the Kloster Seeon monastery near Munich, the meeting will branch out beyond BACE, addressing the function and therapeutic potential of α-, γ- and η-secretases. Register by March 15. A limited number of travel fellowships are available for young investigators travelling from overseas who present a poster.
- Scott Ayton and Ashley Bush on Human and Mouse Microglia React Differently to Amyloid
- Shane Liddelow on Human and Mouse Microglia React Differently to Amyloid
- Wiep Scheper on Does Tau Kill Neurons by Way of Necroptosis?
- Asya Rolls on Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain
- Veronique Miron on Does Tau Kill Neurons by Way of Necroptosis?
- Shijun Zhang on Does Tau Kill Neurons by Way of Necroptosis?
- Steven Finkbeiner on Does Tau Kill Neurons by Way of Necroptosis?
- Howard Weiner and Dennis Selkoe on Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain
- Jonathan Kipnis on Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain
- Eckhard Mandelkow on Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain.
- Arnon Rosenthal on 2019—A Year of Hope for Alzheimer's Research
- Sébastien S. Hébert and Ismael Santa-Maria Perez on Microglial microRNAs mediate sex-specific responses to tau pathology.
- Ralph Nixon on Lysosomal Diseases: Stepping Stones to Gene Therapy for Alzheimer’s?
- Annalisa Pastore on Correction to: Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers.
- Hugo Geerts on At CTAD, Early Failures and Hints of Success, from Small Trials
- Dietmar Thal on A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.
- Heinz Hillen on Picking Through the Rubble, Field Tries to Salvage BACE Inhibitors
- Yunfeng Zheng on Picking Through the Rubble, Field Tries to Salvage BACE Inhibitors
- Charles Glabe on Picking Through the Rubble, Field Tries to Salvage BACE Inhibitors
- Jochen Herms on Picking Through the Rubble, Field Tries to Salvage BACE Inhibitors
- Dietmar Thal and Luís Aragão Gomes on Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer's Disease.