Higher-Resolution Spatial Transcriptomics Maps Mayhem Near Plaques
Microglia within 10 micrometers of Aβ plaques expressed a disease-associated signature. Astrocytes rubbernecked from a bit farther away.
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Too Phatal: How Microglia, Astrocytes Snuff Out Dying Neurons
Live imaging of mouse brain reveals that microglia quickly engulf cell bodies while astrocytes dispose of the neuron’s more distal reaches. The cleanup crew tires with age.
Brain Endothelial Cells Are Diverse, Perturbed by Amyloid
Single-nucleus RNA-Seq of human brain finds regional differences in endothelial cell subtypes. Transcriptomes change in the presence of plaque or vascular amyloid.
APOE Tied to Increased Susceptibility to SARS-CoV-2
People who carry the ApoE4 variant are more likely to succumb to the virus. In vitro, SARS-CoV-2 infects more ApoE4 than ApoE3 brain cells. Astrocytes were activated, neurons degenerated.
Abnormal Tau Slips into Synapses Long Before Tangles Form
More evidence that presynaptic tau may spread from neuron to neuron.
Multiomic Analysis Shows Lysosomes Need Retromer to Stay Healthy
In VSP35 knockout cells, surface proteins get trapped in endolysosomes. They swell with undigested proteins and APP, then spew their contents outside the cell.
Too Basic: APP β-CTF's YENTPY Motif Binds Proton Pump, Thwarts Lysosomes
In cells from people with Down’s syndrome, and in mouse models of DS and Alzheimer’s, excess β-CTF binds vacuolar ATPase, hobbling lysosomal acidification.
Artificial Intelligence Is Everywhere You Look in Dementia Research
As massive, complex datasets burst onto the scene, scientists are using machine learning to analyze the data and uncover hidden patterns. AI may also come in handy in detecting dementia before humans do.
In Human Neurons, ApoE4 Promotes Aβ Production and Tau Phosphorylation
Two papers report that the ApoE4 allele triggers both hallmarks of AD in iPSC-derived cultures, in contrast to its minimal effects in mouse neurons.
In Frontotemporal Lobar Dementia, TDP-43 Snaps into a Chevron Shape
A section of the protein folds on itself to form five layers. Three V-shaped layers cradle each other. This differs from the double-spiral fold in people with FTD/ALS.
With Age, Microglia Pump cGAS, Revving Harmful Inflammation
DNA from leaky mitochondria unleash the cGAS-STING cascade, triggering interferon responses in the brain.
Massive GWAS Meta-Analysis Digs Up Trove of Alzheimer’s Genes
Researchers unearthed 75 risk loci, 42 of them new, and nominated candidate genes for each. A polygenic risk score based on all variants predicted AD risk with high accuracy.
Meet the Two New Biomarker Candidates for Lewy Body Diseases
DOPA decarboxylase in blood or CSF, and damaged mitochondrial DNA in blood cells, separated cases from controls.
Human and Mouse Microglia React Differently to Amyloid
Single-nucleus transcriptomics of postmortem AD brain and mouse models of amyloidosis hammers home the species-specific responses of microglia to Aβ pathology.
At the Core of Microglial Signaling: γ-Secretase
Signaling within microglia requires dozens of substrates of γ-secretase. Without the enzyme, the cells barely react to plaques in mice.
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