Anti-Tau Strategy PACs a Punch
Activating the G protein-coupled receptor PAC1R in the mouse brain prompts the proteasome to clear tangles.
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Activating the G protein-coupled receptor PAC1R in the mouse brain prompts the proteasome to clear tangles.
When pulsed through the skull, ultrasound restored synaptic signaling, neurogenesis, and memory, in old mice.
Biogen got the go-ahead under the FDA’s accelerated approval pathway, which requires change in a surrogate biomarker and Phase 4 studies to verify a clinical benefit.
The L1CAM cell adhesion marker is a widely adopted marker of neuron-derived extracellular vesicles. Except it cannot be found in those teeny packets, claims a new study.
Via recently discovered channels, freshly made monocytes and B cells in the bone marrow of the skull and vertebrae travel directly into the meninges, where they stand ready to infiltrate the brain. These immune cells are distinct from their blood-borne counterparts.
A set of 19 plasma proteins identified clinical Alzheimer’s cases with 97 percent accuracy, and it distinguished mild versus severe dementia. The panel was tested in two small cohorts.
The tau vaccine evoked a robust anti-tau antibody response, which curbed the rise in plasma NfL and CSF p-tau over two years. Cognitive decline continued.
In the face of aging or amyloidosis, microglia lacking C9ORF72 ramped up interferon genes, accumulated lysosomes, and ate synapses.
The anti-tau immunotherapy did not slow cognitive decline among people in the earliest stages of AD, nor did it evoke changes on tau-PET scans.
In mice, disease-associated microglia proliferate so much that they become senescent. Plaques then run amok and synapses are lost.
Industry analysts and watchdogs have heaped criticism on the FDA, while Alzheimer’s researchers remain divided over whether the decision helps or harms the field.
Many Alzheimer’s researchers believe the aducanumab approval heralds the beginning of treatments that slow disease progression—but even they are aghast at the price and hope the drug will not sideline other trials.
Physicians have a new Alzheimer’s treatment option, but most clinics are not ready to administer it. Questions remain about eligibility and insurance, to say nothing of clinician and infusion capacity.
Trial data for aducanumab did not answer key questions, such as how long patients should stay on drug, leaving clinicians around the world to struggle with practical and ethical issues.
Though the first two trial arms were negative on cognition, gantenerumab’s strong effect on biomarkers led to an open-label extension.
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