In a career spanning four decades, Davies spearheaded the cholinergic hypothesis, unlocked secrets of tau, and readily shared antibodies in the field.
While the FDA weighs aducanumab’s marketing license application, Alzheimer’s researchers agree that the agency’s own statistician correctly assessed the data as weak. Most prefer that one more trial be done.
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.
A survey of 16 purported conformation-specific antibodies found that most bound nearly equally well to oligomers and fibrils, and weakly to monomers.
The antiviral protein enhances γ-secretase processing of APP. More of it is present in Alzheimer’s disease.
Carriers of a rare hypomorphic gene variant develop a frontotemporal dementia that features Alzheimer’s-like neurofibrillary tangles.
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.
The panel considered the evidence for efficacy to be weak, and was troubled by too-close collaboration between the sponsor and the FDA.
Learning tests may prove more informative in clinical trials of early AD. A new one claims it can spot a difference in six days.
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.
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.
In mice, accumulation of tau in hilar astrocytes of the dentate gyrus spells trouble for the hippocampus and for spatial memory.
Technical limitations may have misrepresented the transcriptional state of these cells, obscuring detection of their activation signature in frozen postmortem tissue from Alzheimer’s brain.
In mice lacking the recycling protein GGA3, BACE1 trafficking stalls, local Aβ production increases, and axons swell. Does this explain the neuritic dystrophies seen in early AD?
The R1279Q variant of angiotensin-converting enzyme associates with AD and causes neurodegeneration in mice. In a model of amyloidosis, it accelerates decline.