Not the brown trucks with the friendly delivery guys: UPS as in unconventional protein secretion pathway. Tau rides it to slink out of one cell, and, grabbing onto heparin sulfate proteoglycans, enter another.
As RNA Therapies Come of Age, Efficacy Remains Weak At AAN, Sights Set on Antisense Therapies for Diseases of the Brain New Alzheimer’s and Parkinson’s Immunotherapy Data at AAN Will RNA molecules that bump up or tamp down gene expression live up to their
Making deeper inroads into Alzheimer’s systems biology, groups of genes co-expressed in the cortex associated with clinical and pathological traits of the disease, notably the slope of cognitive decline.
Working with human microglia is fraught with technical challenges, but that didn’t stop researchers at Keystone from sharing a flurry of data on how these cells act in neurodegenerative disease.
A Delicate Frontier: Human Microglia Focus of Attention at Keystone TREM2: Diehard Microglial Supporter, Consequences Be DAMed ApoE Has Hand in Alzheimer’s Beyond Aβ, Beyond the Brain Synaptic Tau Clangs the Dinner Bell for Hungry Microglia VCAM1: Gateway
At Keystone, the work of several groups painted TREM2 as a dedicated supporter of microglial function across neurodegenerative disease models, including those for ALS.
At a Keystone meeting, researchers agreed that ApoE stokes damaging neuroinflammation in response to tau pathology. The E4 allele ramped up cholesterol biosynthesis in microglia and astrocytes, and even promoted neuronal damage when expressed outside of the brain.
In knockouts that model the most severe form of Gaucher’s disease, replacing one gene calms neuroinflammation, reduces neurodegeneration, and extends lifespan.
Oligonucleotides that suppress SOD1, and small molecules that limit its binding to the protein Derlin-1, delay disease onset and extend lifespan in rodent models of ALS.
BAN2401 Removes Brain Amyloid, Possibly Slows Cognitive Decline On Target: Crenezumab Reduces Aβ Oligomers in CSF PET Ligand Lights Up AAIC, May Detect Synapse Loss in AD Could Better Blood Pressure Management Preserve Cognition? Focused Ultrasound Breach