Alzheimer’s Microglial Risk Gene INPP5D Revs Up Inflammasome
In AD brain, microglia make less of the full-length protein. Loss of INPP5D releases the brakes on inflammation, and may spur microglial phagocytosis.
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Brain of Woman Who Died on Leqembi Shows Worst-Case Scenario
The patient, an APOE4 homozygote with severe cerebral amyloid angiopathy, developed vascular inflammation and bleeding throughout her brain.
Mind the GAP—Synaptic Protein in CSF Signals Tau Spread
Growth-associated protein 43 in the CSF identified people who accumulated tangles fastest. These spread through connected brain regions.
Epigenetic Shenanigans—In AD, Chromatin Opens Up in Blood Immune Cells
In CD8+ T cells and monocytes, DNA was more accessible in people with AD and even more so in ApoE4 carriers.
First Whole-Genome Sequencing of PSP Nets Six New Risk Loci
ApoE2 reported as raising risk for progressive supranuclear palsy, a rare tauopathy.
API Colombian Trial of Crenezumab Missed Primary Endpoints
Topline results showed no statistically significant slowing of decline on either of two primary endpoints. Trends across multiple endpoints favored crenezumab.
Exposure, Exposure, Exposure? At CTAD, Aducanumab Scientists Make a Case
Biogen researchers claim the antibody worked in people who got enough of it. To other researchers, the signal validates the amyloid hypothesis and injects fresh energy into the field. But is this interrupted dataset enough to approve?
Roche Pulls Plug on Two Phase 3 Trials of Crenezumab
An interim analysis predicted the antibody would not slow Alzheimer’s progression; a crenezumab trial in autosomal-dominant AD is continuing.
Estimates of Young-Onset Dementia Prevalence Just Doubled
A meta-analysis of 2.8 million people estimates 119 in 100,000 develop dementia before age 64—twice the previous estimates. Prevalence increases with age and strikes men and women equally.
Do Overloaded Microglia Smother Stressed Neurons?
In mice with prion disease, microglia shifted from gobbling up misfolded protein to engulfing flagging neurons. This change coincided with symptom onset.
Cancer Treatment Takes Aim at Tauopathy
Building on results in AD mouse models, researchers now report that immune checkpoint inhibitors reduce pathology and improve cognition in tauopathy mice, too. Other scientists are skeptical.
A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque
The fateful pairing may happen in microglial lysosomes, where ApoE forms fibrillar aggregates.
Legacy of A4 Secondary Prevention Study Goes Beyond Negative Result
The decade-long trial found no benefit for solanezumab in delaying progression, but laid the groundwork for subsequent prevention studies.
Mutant AβPP Retards Growth in Hippocampus before Plaques Form
Collaborative research directed by Floyd E. Bloom of Neurome Inc. and the Scripps Research Institute shows that dramatic changes occur in the brains of mice expressing mutant human forms of AβPP long before any Aβ has been deposited...
Trials and Tribulations: Does ADAPT Have to Adapt?
Researchers working on NSAIDs as potential treatments for AD are discussing whether a large ongoing prevention trial of two such anti-inflammatories is testing the right drugs.
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