Proteomics Dates Endosomal, Synaptic Changes to Preclinical AD
In postmortem brain, proteins involved in all manner of vesicular functions waxed or waned with increasing phases of disease, starting years prior to symptoms.
In postmortem brain, proteins involved in all manner of vesicular functions waxed or waned with increasing phases of disease, starting years prior to symptoms.
Instead of chewing up and disposing of the amyloid they ingest, microglia appear to compact it, then spit it back out as dense-core plaque.
Sending low-intensity, gamma frequency electric current through the brain boosted short-term memory, perhaps by increasing cholinergic transmission.
Herpes 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.
In early stage trials, light and sound promoted neuronal communication, calmed immune cells, and slowed brain atrophy, but cognitive benefit remains unclear.
After news on “new data” they won’t see, three committee members argue against approval.
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.
When microglia in a mouse model of amyloidosis lose the ability to phagocytose, fewer plaques form. This unexpected finding supports the idea that microglia build plaques, rather than disposing of them. New data suggests they take up amyloid protofibrils on the perimeter of plaques, compact them in their lysosomes, and spit them back out, or die and release them in this way. The data may inspire scientists to re-examine how to approach Alzheimer’s therapy.
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.
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