From Treadmills to Transcriptomes: Consortium Charts Molecular Responses to Exercise
First papers from MoTrPAC initiative report myriad responses to endurance training in multiple organs in rats, including the brain and heart.
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In ADAD, Plaque Removal Improves Synaptic and Inflammatory Biomarkers
In the DIAN familial AD prevention trial, plaque-busting antibody gantenerumab, but not monomer-targeting solanezumab, nudged fluid markers toward normal.
Stirred by Tau, Neurons Amp Up Lipid Droplets in Glia
Tauopathy cranks up lipid synthesis in neurons, which slip the fats to microglia. Blocking AMP kinase greases this process.
APP C-Terminal Fragments Stifle Calcium Flow from ER to Lysosomes
Amyloid precursor protein CTFs accumulate in lysosomes adjacent to endoplasmic reticulum. This disrupts calcium flow between the organelles.
Two Paths for TREM2-Positive Microglia: DAM or Senescence?
Scientists find the senescent subtype has a distinct protein signature, but little change in gene expression, causing it to be overlooked in transcriptomic studies.
Axons or Bust: To Reach Neuron Extremities, RNAs Hitch a Ride on Lysosomes
Lysosomes deliver a plethora of mRNA transcripts, including those encoding ribosomal subunits and mitochondrial proteins, to axonal terminals for translation.
Diabetes Drug Shows Promise for Parkinson’s Disease
In a small Phase 2 trial, the GLP-1 analogue lixisenatide stabilized motor abilities over one year in people with early PD.
Could New Alzheimer’s Marker p-Tau212 Rival p-Tau217?
In preliminary studies in five cohorts, the two markers have similar diagnostic accuracy, and stain tangles in postmortem brain equally well.
Tau Toggling Peptides: One Seeds Fibrils; the Other Dismantles Them
Two studies describe how small peptides that latch onto tau have an outsize impact on fibrillization of the protein. Both point to therapeutic strategies.
Rubbing Microglia the Right Way? At ADPD, Scientists Showcase New Strategies
Preclinical studies and early phase trials target microglial receptors CD33 and TREM2, and amyloid-stoking ASC specks.
Over the Span of AD, Roles of Astrocytes and Microglia Change
Reactive astrocytes spell trouble for synapses, while microglial transform from protective to destructive as disease progresses.
Could Sumoylation Take Down Tangles?
The addition of SUMO2 to tau prevents its phosphorylation and aggregation, preserving synapses and memory in tauopathy mouse models.
Easing Microglial Brakes Alleviates Amyloid Pathology in Mice
An antibody against the inhibitory receptor LILRB4 prevented its binding to ApoE. The upshot? Microglia engulfed more Aβ fibrils and plaque load fell.
p-Tau217 Immunotherapy Alleviates Tangle Pathology in Mice
Two antibodies—one against the phosphoprotein, the other to tau’s N-terminus—restored proteostasis in the brain.
Multiple Strategies Seek to Banish α-Synuclein Aggregates
At AD/PD, scientists presented small molecules that break up fibrils and antibodies that target pathogenic forms of α-synuclein or hinder spread in iPSCs and mice.
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