Piezo1 Steers Microglia Toward Rigid Aβ Plaques
Without this mechanosensor, microglia slowly respond to plaques. In mice, a Piezo1 agonist bolstered plaque containment and lowered amyloid burden.
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Meddling Medin: A Vascular Amyloid That Promotes CAA?
In mice, this glycoprotein fragment accelerated amyloid deposition in cerebral blood vessels; in people, higher levels correlated with faster cognitive decline and greater AD risk.
Sans TREM2, ApoE4 Drives Microgliosis and Atrophy in Tauopathy Model
Phospho-tau and tangles accumulated, microglia bloated with lipids, and the brain atrophied in these mice.
Gantenerumab Falls Short in Phase 3
The antibody removed less plaque than expected and did not slow cognitive decline, according to top-line data. Detailed data to come at CTAD.
Perivascular Macrophages: New Target in Aging and Alzheimer’s Disease?
These unassuming cells keep cerebral vessels supple, forcing CSF through the brain and clearing Aβ. Their abilities wane with age, but can be restored.
Gene Networks That Control Astrocyte Diversity Linked to AD
Brain-wide transcriptomics identified genes that characterize astrocytes by anatomical region and morphology. Some are risk genes for neurodegeneration.
Short Aβ Fibrils Easily Isolated from Alzheimer's Brain Fluid
Once assumed to be high-molecular-weight oligomers, these short, diffusible fibrils share the same structure as their plaque-bound counterparts. Both bind lecanemab.
Cornucopia: LOADs of New Mouse Models Available
Scientists now have more options to model late-onset Alzheimer’s disease. APOE, TREM2, and gene combinations better mimic LOAD than do models of familial AD.
KOLF2.1J: The Mother of All iPSC Lines?
The iPSC Neurodegenerative Disease Institute proposes a reference iPSC line to standardize research between labs.
SYK It To ’Em: Kinase Enables Microglia to Clear Plaques
Sans SYK, mice struggle to mobilize disease-associated microglia or reign in amyloid or myelin fragments.
In Mice, TREM2 Antibody Mobilizes Microglia, Yet Worsens Tangles
Activating the microglial receptor also left amyloid untouched, despite prompting microglia to surround plaques.
Human Microglia Mount Multipronged Response to AD Pathology
Two different model systems catalogued cell states: DAM-like, antigen-presenting, cytokine-, and interferon-based. More work is needed to pin down function.
In TRAILBLAZER, Plasma GFAP Falls, but NfL Continues to Rise
While GFAP seems a sensitive biomarker of Aβ plaque removal, NfL might respond more slowly.
In Cultured Human Neurons, Aβ Spurs Synapse Growth
While the familial Swedish AD mutation spurred synaptic growth, BACE inhibition, or APP deletion, had the opposite effect.
“Numbing" Neurons Temper Tau in Mice
Without the trafficking protein Numb, tau accumulated in retinal ganglion cells and motor neurons, accelerating hind limb paralysis.
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