New Ways to Target Aβ and BACE Show Promising Phase 1 Data
BACE inhibitors are shaping up; pyroglutamate Aβ antibody clears plaques without ARIA, but immune reaction raises a flag.
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RIP: Serotonin Receptor 5-HT6 Antagonist
Publication of negative results of Phase 3 idalopirdine trials lays to rest yet another candidate drug.
Most Detailed Look Yet at Activation States of Human Microglia
Single-cell RNA sequencing of 16,000 live microglia freshly isolated from human brain reveals nine distinct subtypes. One fades in Alzheimer’s. Why?
Mounting Modifications Move Tau Toward Aggregation in Alzheimer’s Brain
Quantifying 95 post-translational modifications of tau extracted from AD and control brains, a proteomics study proposes a “processive” model of phosphorylation, ubiquitination, acetylation that drive aggregation and map to distinct stages of disease.
Fatal Gift Wrap: Neurons Fall for Packaged Tau Oligomers
Neurons take up extracellular vesicles containing tau oligomers more readily than they do free tau. Some gift: This speeds the march of tauopathy through mouse brain.
Aβ Binds Glutamate Receptors. Only in Guys, Though.
In both mice and (wo)men, the sex difference comes down to an Aβ-glutamate receptor-prion protein troika.
Proteomics Uncovers Potential Markers, Subtypes of Alzheimer’s
Changes in the composition of the cerebrospinal fluid and synapses may reveal novel insights into AD pathology.
Herpes Triggers Amyloid—Could This Virus Fuel Alzheimer’s?
Herpes viruses that are commonly found in human brain promote rapid Aβ fibrillization and deposition in AD model systems.
Do Lysosomes Help Propagate Tau Seeds?
In cultured cells, lysosomal activity was necessary to enable tau seeds to break out of internalized exosomes and trigger the aggregation of tau in the cytosol.
Does TYROBP-ApoE Signaling Work Independently of TREM2?
This pathway may transmogrify microglia during neurodegeneration, without the help of TREM2.
New Data from Past BACE Inhibitor Trials Shed Light on Side Effects
The brain shrinkage due to verubecestat emerged quickly but did not worsen or cause neurodegeneration. Curiously, both verubecestat and lanabecestat dulled episodic memory and boosted verbal fluency.
Fits and Starts: Trial Results from the CTAD Conference
In Barcelona, data ran the gamut from a few hopeful little hints on new treatments to mixed signals on familiar players, and failed drugs thrown on the scrap heap.
Doubling Rab5 in Mice Leads to Neurodegeneration—Without Plaques
Overexpressing the endosomal activator in neurons not only caused those organelles to swell, but also bungled synaptic transmission, goaded hyperphosphorylation of tau, and destroyed cholinergic neurons.
Expression Analysis Uncovers Three Distinct Forms of Alzheimer’s
High amyloid burden and neuroinflammation, neuronal excitability, and tangles and oligodendrocyte loss distinguish the disease types.
Plasma P-Tau181 Predicts, Monitors Alzheimer’s Progression
The blood-based marker may be far more scalable and cost-effective for tracking the disease than PET imaging and CSF biomarkers.
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