Of Four Aβ Antibodies, Only Aducanumab Stems Tide of Toxic Oligomers
While one anti-Aβ antibody thwarts initial seeding of fibrils, and others keep fibrils from lengthening, aducanumab prevents oligomers forming on their surface. In vitro, that is.
NEWS
Introducing the Coarse-Grained Plaque—A New Type of Amyloid
Comprising mostly Aβ40, these large plaques are shot through with strange tubular structures and BBB markers. They are common in early onset AD.
Nixing TMEM106b Fans the Flames of Progranulin Deficiency
Three studies agree that TMEM106b/progranulin double knockouts develop more extreme lysosomal dysfunction, inflammation, and motor deficits than PGRN KOs.
Protective AD Variant Pinpoints Sweet Spot for Microglial Activation
Phospholipase C-γ2 acts downstream of TREM2 to rev up beneficial inflammation, phagocytosis, and cell survival.
Could Contaminated Scalpels Seed Amyloidosis?
A panel of experts concludes the evidence for this scary prospect is weak, but recommends neurosurgeons use separate neurosurgical instruments for young and old patients. The experts called for further studies.
In Preclinical Alzheimer’s, Learning Falters Before Memory
Learning tests may prove more informative in clinical trials of early AD. A new one claims it can spot a difference in six days.
Mutation in the Parkinson’s Gene DJ-1 Derails Splicing
Restoring proper gene editing assuaged mitochondrial defects in patient-derived neurons and organoids. Splicing errors may underlie other PD cases as well.
Micro Nudge? Positive Phase 2 Results for ALS Combination Drug
AMX0035, a mix of sodium phenylbutyrate and taurursodiol, slowed functional decline over six months by about as much as the approved ALS drug edaravone.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Abcam, BrainXell, and the Jackson Laboratory.
SPOTLIGHT
Antibodies Throw Wrench into Aβ Assembly Line
Sure, all anti-Aβ antibodies hobble some aspect of the peptide’s aggregation, but a head-to-head comparison of four investigational monoclonals turned up dramatically different mechanisms. While solanezumab stopped new fibrils from forming in the first place, gantenerumab and bapineuzumab kept fibrils from getting longer. Aducanumab sabotaged secondary nucleation, the process whereby fibrils catalyze the formation of new oligomers, the most toxic of Aβ species.
Behold, the Coarse-Grained Plaque
Pathologists have newly characterized a beefy type of plaque that seems distinct from cotton-wool and dense-core plaques. Coarse-grained plaques, as they are called, can grow to be a tenth of a millimeter across. They associate with blood vessels and are more common in early onset AD and in people who carry two copies of ApoE4. They could help researchers understand the origin of amyloid plaques.
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