Do Lysosomes Help Propagate Tau Seeds?
In cultured cells, lysosomal activity was necessary to enable tau seeds to break out of internalized exosomes and trigger the aggregation of tau in the cytosol.
NEWS
Expression Analysis Uncovers Three Distinct Forms of Alzheimer’s
High amyloid burden and neuroinflammation, neuronal excitability, and tangles and oligodendrocyte loss distinguish the disease types.
In Phase 2, Donanemab Curbs Cognitive Decline in Early Alzheimer’s
Among people with early AD, the monoclonal antibody wiped out Aβ plaques and slowed cognitive and functional decline by a third, relative to placebo.
Doubling Rab5 in Mice Leads to Neurodegeneration—Without Plaques
Overexpressing the endosomal activator in neurons not only caused those organelles to swell, but also bungled synaptic transmission, goaded hyperphosphorylation of tau, and destroyed cholinergic neurons.
Does TYROBP-ApoE Signaling Work Independently of TREM2?
This pathway may transmogrify microglia during neurodegeneration, without the help of TREM2.
Begone 2020: Despite COVID, Alzheimer’s Research Advanced
Confronting unprecedented challenges this past year, scientists found ways to tide their research over and keep clinical trials mostly on track.
Aβ Binds Glutamate Receptors. Only in Guys, Though.
In both mice and (wo)men, the sex difference comes down to an Aβ-glutamate receptor-prion protein troika.
In People Who Defy ApoE, New Alzheimer’s Risk Genes Found
Researchers identified genetic variants that may explain why some ApoE4 carriers remain free of Alzheimer’s, while some ApoE2 carriers do not.
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.
SPOTLIGHT
Do Broken Lysosomes Spill Tau Seeds?
Tiny vesicles known as exosomes ferry aggregated tau between cells, helping to spread pathology. But how does their cargo escape? Ironically, the key lies in the robustness of exosomes, according to a new study. Once internalized, they end up inside lysosomes, which struggle to break them down. In the process, the lysosome makes more acid and ruptures, spilling tau seeds into the cytosol where they trigger new deposits.
Does Endosomal Dysfunction Drive Alzheimer’s?
In the earliest stages of Alzheimer’s disease, neurons become clogged with swollen endosomes. Can this pathology drive the neurodegenerative cascade, even without Aβ plaques? This seems to be the case in mice that mildly overexpress the endosomal activator Rab5. Their synapses shrank, tau became hyperphosphorylated, and cholinergic neurons degenerated. In extensive commentary, researchers weighed in on what the findings do—and do not—say about the role of endolysosomal dysfunction and Aβ in AD pathogenesis.
Begone 2020: Despite COVID, Alzheimer’s Research Advanced
Phew. It is finally behind us. While Covid-19 made us dread 2020, let’s also remember that this challenging year brought progress in the fields of Alzheimer’s and related dementias. Lest we move on too fast, Alzforum’s annual retrospective captures some of last year’s highs and lows. Yes, it’s long. But, dear reader, where are you going to go besides your home office or the line at the grocery store? In both places, it’s a good read.
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