Research Roundup #4 – APP, amyloid-β, and a neuron-glia communication hub

By Alomone Team • October 2021

There’s a great selection for you in this Research Roundup. We look at some new and interesting roles for amyloid precursor protein (APP) amyloid beta (Aβ or Abeta) in Alzheimer’s disease, and also how the nodes of Ranvier seem to be places where glia and neurons communicate to regulate neurotransmission.

Amyloid precursor protein essential to regulate inhibitory neurotransmission

APP is somewhat enigmatic. It’s a highly conserved, single-pass transmembrane protein and its physiological function is a bit of a mystery, but it does play a role in initiating Alzheimer’s disease. Recently, scientists from Brussels looked at how APP might modulate excitatory and/or inhibitory GABAergic signaling. They overexpressed wild-type human APP in mice and found that it results in early cognitive impairment, neuronal loss, and electrophysiological abnormalities like increased long-term potentiation. Interestingly, all of this happened without the presence of amyloid plaques or changes to GABAergic and glutamatergic neurons.

Amyloid-b linked to tau hyperphosphorylation in Alzheimer’s disease

From APP in Alzheimer’s disease to Ab. The leading theory of AD pathogenesis right now is soluble oligomers of Aβ (Aβ_o) accumulate and trigger a cascade of events, which includes key changes in tau (like hyperphosphorylation) that drive disease development. But Aβ_o’s tau-recruitment and how that might result in tau’s hyperphosphorylation are unknown. A team from Oxford has begun to figure that very thing out. Their work uncovers a pathway that links Aβ_o to tau hyperphosphorylation. It shows how it’s a higher neuronal glutamate release probability that increases the magnitude of long-term depression in the hippocampus, which in turn drives tau hyperphosphorylation. There’s some great stuff in this paper – more than a summary can do justice – and it’s filling major gaps in our understanding of Alzheimer’s disease.

Explore this great paper at Cell Reports

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Nodes of Ranvier could be a neuro-glial communication hub

Microglia have plenty of different roles to play, such as brain plasticity and homeostasis, neuronal loss and neuroprotection, and myelin regeneration in diseases like multiple sclerosis. We also know that microglia can sense neuron activity modulate their function but how this communication happens is largely unknown. But new work out of Paris, which makes extensive use of neuroimaging, suggests that it’s within the nodes of Ranvier that microglia-neuron talk is happening. Microglia in this setting might also modulate neuronal survival and remyelination.

Hear more about chatter at the node of Ranvier in Nature Communications