In People Who Defy ApoE, New Alzheimer’s Risk Genes Found
Researchers identified genetic variants that may explain why some ApoE4 carriers remain free of Alzheimer’s, while some ApoE2 carriers do not.
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Huntingtin Repeats Cause—FTD, Caveolin Variants—ALS?
Breaking familiar gene-disease patterns, HTT trinucleotide expansions lead to huntingtin aggregates in prefrontal cortex. Noncoding caveolin 1 variants suppress its expression.
Not Just a Biomarker: YKL-40 Links Glial Clock to Amyloidosis
This astrocytic glycoprotein greases glial phagocytosis and reduces plaque burden in mice. The circadian clock protein Bmal1 suppresses it.
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.
Positive Phase 2 Results Claimed for Masitinib in Alzheimer’s
Topline results suggested that the anti-inflammatory treatment stabilized cognition and function over six months. The trial did not include biomarkers.
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.
Epoxide Hydrolase, a Fat New Target for Alzheimer’s Therapy?
The enzyme degrades anti-inflammatory fatty acids in the brain. Blocking it with a brain-penetrant small molecule calmed A1 astrocytes, synapse-eating microglia, and improved amyloidosis and cognition in a mouse model.
MTBR-243 Tau: A Fluid Biomarker for Tangles Themselves?
Researchers found that bits of tau from the protein’s microtubule-binding region can be detected in the cerebrospinal fluid. These, not phospho-tau or total tau, reflect neurofibrillary tangles in the Alzheimer’s brain.
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.
You Are What You Breathe: Polluted Air Tied to Plaques, Brain Atrophy
Two cohorts—IDEAS and WHIMS—show Aβ accumulation and brain shrinkage in cognitively normal and impaired elderly who were exposed to levels of air pollution even within current EPA limits.
Biomarkers of Errant Endosome Spotted in Cerebrospinal Fluid
In mice, forebrain neurons with hobbled retromers ooze fragments of tau and several BACE1 substrates into the CSF. Similar proteins are up in CSF from people with MCI and Alzheimer’s disease.
Plasma NT1: This Tau Snippet Predicts Cognitive Decline in Alzheimer’s
Among a growing number of blood-based tauopathy markers, this new immunoassay may offer a way to catch preclinical disease just before symptoms show up.
Microglia in Tauopathy: Not Just Homeostatic Versus DAM
In mouse models of tauopathy, microglia populations are far from binary. Different activation stages emerge at different phases of disease, some marked by viral defense pathways.
In the United States, Racial Disparities in Dementia Risk Persist
Despite overall falling dementia rates in the U.S., black people remain more susceptible than whites.
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