Double Whammy: APP Uppsala Deletion Ups Aβ and Its Aggregation Propensity
Found in one Swedish family, this mutation speeds up plaque deposition by way of two different mechanisms, leading to disease onset as young as age 40.
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ADAD and LOAD: At Cellular Level, They Are Not the Same
Single-nuclei expression analysis identified different cell clusters from people who carried autosomal-dominant Alzheimer’s mutations or risk variants for late-onset AD. Also, microglia RNA-Seq goes big.
Up-and-Coming Immunotherapies Target Aβ and Tau
Scientists are testing passive and active immunotherapies that take down pyroglutamate Aβ, and a combo Aβ/tau vaccine.
AL001 Boosts Progranulin. Does it Slow Frontotemporal Dementia?
In an open-label Phase 2 study, fluid biomarkers suggested the anti-sortilin antibody restored lysosomal function and reduced neuroinflammation in people with symptomatic FTD. Tantalizingly, participants worsened less than historical controls.
Flurry of Investigations Besets Aducanumab
In the wake of the controversial thumbs-up for Aduhelm, the U.S. federal government is probing not only aducanumab’s price and approval history, but also the FDA’s accelerated approval pathway in general.
Aduhelm Approval Reverberates Through Research
Scientists worry about trial recruitment and retention, and discuss whether upcoming trials should allow aducanumab as a background therapy.
Lecanemab Post Hoc: Is Continual Treatment Required for Cognitive Benefit?
Patients taken off the drug continue to outperform those who were never on it, and decline slows even more once treatment resumes. Cognition and plasma Aβ changes are consistent with disease-modifying effect.
Will Insurance Cover Aducanumab? Jury Is Out
While payers public and private are deliberating whether or not to cover this first-in-class drug, the health economics group ICER re-affirms its original conclusion that aducanumab is overpriced.
Seeking Real-World Data on Whether Aducanumab Works
Biogen sponsors an observational study on the drug’s effects; no word yet on the FDA-required Phase 4 trial. Meanwhile, researchers suggest other ways to test efficacy.
Antisense Therapy Stifles CSF Tau in Mild Alzheimer’s Disease
Initial results from the first trial of an antisense oligonucleotide against tau in Alzheimer’s are in. BIIB080 appears safe and curbed total tau and phospho-tau 181 levels in the CSF. Clinical outcomes were not assessed.
On Donanemab, Plaques Plummet. Off Donanemab, They Stay Away
Data from a Phase 2 trial also suggested that when amyloid dropped in treated brain, plasma p-tau217 followed suit. Using a CAMD progression model, Lilly claims the biomarker responses correlated with slower decline.
Aducanumab: Will Appropriate-Use Recommendations Speed Uptake?
At AAIC, leading Alzheimer’s clinicians plug gaps in the FDA label. They urge exclusion of people with cerebrovascular risk, and an MRI monitoring bonanza. Meanwhile, clinical rollout starts slow, with major hospitals declining to administer.
Alzheimer's Association International Conference- 2021
Aducanumab: Will Appropriate-Use Recommendations Speed Uptake? On Donanemab, Plaques Plummet. Off Donanemab, They Stay Away Antisense Therapy Stifles CSF Tau in Mild Alzheimer’s Disease Seeking Real-World Data on Whether Aducanumab Works Will Insurance Co
Astrocytes Are Just Dying to Spread Tau
Senescent astrocytes spew HMGB1, a harbinger of cell death. Blocking this release prevented cell senescence, reduced neurofibrillary tangles, and improved memory in mice.
Microglia in Health and Disease
Alzforum readers might be forgiven for thinking all microglia do is act prominently, if mysteriously, in Alzheimer's pathogenesis. Not so. A recent flurry of papers shows that microglia can match themselves specifically to GABA synapses. They can rev
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