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.
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VCP Coding Mutation Causes a Tauopathy With Vacuoles
Carriers of a rare hypomorphic gene variant develop a frontotemporal dementia that features Alzheimer’s-like neurofibrillary tangles.
In Astrocytes, ApoE4 Bungles Endocytosis, PICALM Picks Up the Slack
The first steps of endocytosis faltered in astrocytes expressing ApoE4, but pumping in PICALM reversed the problem. A new study places two Alzheimer’s risk factors into the same cellular mechanism.
FDA Advisory Committee Throws Cold Water on Aducanumab Filing
The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
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.
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?
Even Without Amyloid, ApoE4 Weakens Blood-Brain Barrier, Cognition
Hippocampal imaging and fluid markers of BBB damage found in ApoE4 carriers.
Social Distancing Shutters Alzheimer’s Research
With experiments and careers on hold, scientists working from home are turning to virtual lab meetings and journal clubs to keep up morale.
Human Blood-Brain Barrier Model Blames Pericytes for CAA
When these tiny mural cells carried APOE4, they secreted more ApoE, causing Aβ to deposit in capillary walls. Blocking ApoE production prevented angiopathy.
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.
Widely Used Tau Seeding Assay Challenged
According to a structural analysis, fluorescently tagged tau fragments cannot form paired helical filaments. This suggests the assay does not measure prion-like propagation.
Does Phosphorylation of Presenilin 1 Drive Microglial Migration, Aβ Clearance?
In mice with defective PS1 phosphorylation, microglial autophagy falters, exacerbating Aβ burden.
Molecular Structure of LRRK2 Gives Clues to Parkinson’s
The first high-resolution look at LRRK2 implies that pathogenic mutations increase binding to microtubules by biasing the kinase domain toward a closed, active conformation.
In ALS and FTD, Two Different Routes to TDP-43 Aggregation
A C9ORF72 polydipeptide repeat induces aggregation by direct interaction with TDP-43, while progranulin mutations that trigger microglial toxicity cause TDP-43 to accumulate via complement.
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.
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