At AD/PD, researchers reported that low-intensity electric current sent through the brain at gamma frequency restored cholinergic transmission and boosted short-term memory.
Data from France and Germany bolster the proposed link between herpes virus and Alzheimer’s. Infection upped risk in ApoE4 carriers, damaged brain tissue, and correlated with neurodegeneration markers in the CSF.
Disruption of the membraneless organelles may explain toxicity of tau aggregates.
In cell culture, neurons with the strongest expression of cell-cycle proteins survived best in the presence of Aβ oligomers, hinting at a protective effect.
Based on early stage trials, scientists at AD/PD said that light and sound can promote neuronal communication, calm immune cells, and slow brain atrophy. On cognitive outcomes, the jury is still out.
After news on “new data” they won’t see, three committee members penned an editorial laying out their argument against approval. The agency is expected to decide on the licensing application by June.
In therapy-like paradigm, suppressing ApoE4 in astrocytes toned down tauopathy. This assuaged microglia, neurodegeneration, and revived nest-building.
New research implicates IL-6 signaling and even Aβ42 itself as BACE targets, complicating efforts to resurrect BACE inhibitors at a low dose.
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.
Can electric current spark better memory in people with mild cognitive impairment? Possibly, according to researchers—at least short-term. In a pilot study, people with MCI received transcranial alternating current stimulation (tACS), a low-intensity electric current therapy, set at a gamma frequency of 40 Hz. After a one-hour session, they recalled more words, matched more names to faces, and had improved cholinergic signaling compared to people who got sham treatment. Whether this was mediated by gamma entrainment will be tested in a larger trial.
Two presentations at the AD/PD 2021 conference appear to strengthen the proposed link between herpes simplex virus and Alzheimer’s disease. In a French study, herpes infection bumped up AD risk in ApoE4 carriers but not noncarriers. Damaged white matter and ever-so-slightly smaller hippocampi were discerned in infected people of all ApoE genotypes. In a German study, higher CSF herpes antibody titers tracked with CSF p-tau in people with mild AD.
If enhancing cognition with light and sound seems futuristic, then welcome to the future. Or so some scientists say. Results from four early stage clinical studies on mild Alzheimer’s disease were presented at the virtual AD/PD 2021 conference. The studies used two related approaches to modulate brain waves. Both reportedly synchronized neural firing in the gamma frequency range, harmonized neuronal connections, shifted the brain’s cytokine profile, and slowed brain atrophy. Memory and functional measures gave mixed results.
ApoE4, the strongest genetic risk factor for late-onset AD, is known to exacerbate the havoc caused by tau pathology. Now, researchers report that removing ApoE4 only from astrocytes assuages neurodegeneration, tau pathology, and even keeps microglia from devouring synapses. The findings paint astrocytic ApoE as an orchestrator of neurodegeneration.
BACE Inhibition: Not Quite Dead, But Complicated
Research presented at the 2021 AD/PD conference provides a glimmer of hope for BACE inhibitor therapy. Full data from the terminated Phase 3 elenbecestat trials finds no cognitive deficit, demonstrating that this side effect can be avoided. Meanwhile, basic research turns up a new BACE1 substrate, Gp130, which may affect synaptic transmission through IL-6 signaling. Other evidence implicates BACE1 in degrading Ab42, as well as forming it, suggesting inhibitor dosing might have to balance these roles. Altogether, BACE experts still see a pathway for low-dose BACE inhibition as a preventative strategy. Read Madolyn Bowman Rogers’ Drop of Hope? No Cognitive Worsening on BACE Inhibitor and What BACE Hits: New Substrates Create New Headaches.
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