11170 RESULTS
COMMENT This highly interesting study supports an important role of sumoylation as a post-translational modification that solubilizes aggregation prone proteins. The study focuses on SUMO2, and it will be interesting to see how modification by SUMO2 compares to m
COMMENT It’s been almost a decade since the exciting initial discovery of tau SUMOylation by SUMO1, which inhibits degradation of tau and promotes its accumulation. However, it is unknown whether other SUMO isoforms have a similar role. Perhaps surprisingly, thes
COMMENT This is an exciting study by Hou and colleagues showing that modulating LILRB4 using an antibody likely inhibits LILRB4 binding to APOE, activating microglia and attenuating Aβ-related measures, such as plaque load and neuronal dystrophy. This study follo
COMMENT Microglia with unique transcriptional signatures have been identified in Alzheimer’s disease patients and animal models (Keren-Shaul et al., 2017). Understanding the regulation and impact of these states is essential if we want to know how to modulate mic
COMMENT This is very interesting work, as it dives into the plethora of receptors that control microglial function. For very good reasons, the field has focused extensively on some specific molecules, such as TREM2 or CD33, but microglia express a vast diversity
COMMENT Lecanemab did not work for women, which is bad news because there are twice as many women as men with AD. Lecanemab did not work for APOE4 carriers, which is bad news for AD patients, 60–75 percent of whom have one or two APOE4 genes. Remarkably, for some
COMMENT The original paper on the App-SAA knock-in mouse model of Alzheimer’s disease (JAX: 034711) reported that FDG-PET uptake, a surrogate for glucose utilization in brain, revealed cortical hypermetabolism across the studied lifespan of 5-20 months in homozyg
COMMENT A word of caution for those who are trying to extract biological meaning from tau RD biosensor cell lines: Nuclear tau aggregates are an artifact of the truncation used in the model. Disease-relevant full-length tau aggregates never localize to the nucleu
COMMENT In Parkinson’s as in Alzheimer’s disease, biological markers are important to improve early diagnostics. This paper provides strong evidence that cutaneous phosphorylated α-synuclein may serve as diagnostic biomarker for Parkinson’s disease (PD), dementia
COMMENT This study confirms previous smaller studies showing that the levels of phosphorylated α-synuclein are increased in peripheral nerve terminals in the skin in neurological diseases characterized by accumulation of α-synuclein aggregates in the brain. The s
COMMENT In this comprehensive work by the de Jager team, the authors addressed the effects of genetic variants on cell type- and cell subtype-specific gene expression in human brains. Using a large number of human brains and a wealth of genetic and new single-nuc
COMMENT Divide and Conquer: Compartmentalization of the Brain’s Subarachnoid Space Facilitates Rapid Periarterial CSF Flow Over the past decade, there has been significant interest in comprehending the underlying anatomy and physiological mechanisms that regulate
COMMENT This is an exciting study—it provides the first view into tracer movement through the human subarachnoid space over just a few hours. They find that tracers move in a specific pathway along the arteries before entering brain tissue. This information is im
COMMENT This may have been the fourth randomized Phase 3 trial of a form of methylene blue in various doses by this company. None was statistically significant compared to their contemporaneous controls. The trials used a small dose of HMTM or similar as the cont
COMMENT The saga of “methylene blue,” or derivatives of this dye with various names, including LMT-X/LMTM and HMTM, continues with a presentation of TauRx-sponsored work at ADPD 2024. The history of this drug, which putatively targets tau aggregation at low doses
