Research ArticleAlzheimer’s Disease

Activation of CaMKIV by soluble amyloid-β1–42 impedes trafficking of axonal vesicles and impairs activity-dependent synaptogenesis

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Sci. Signal.  11 Jul 2017:
Vol. 10, Issue 487, eaam8661
DOI: 10.1126/scisignal.aam8661

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Amyloid-β and intersynaptic trafficking

Synaptic loss and dysfunction as well as neuronal accumulation of amyloid-β (Aβ) are classic features of Alzheimer’s disease (AD). Synaptic components are transported along axons in actin- and synapsin-associated vesicles to adjust synaptic strength in response to activity and to promote the formation of new synapses. Using hippocampal neurons isolated from rats and mouse models of AD, Park et al. found that a soluble form of Aβ impedes Ca2+ clearance from neurons, which led to activation of the kinase CaMKIV. CaMKIV-mediated phosphorylation of synapsin caused its dissociation from synaptic vesicles and actin, thereby impairing vesicular transport. Targeting this pathway might suppress the pathological effects of Aβ in patients with AD.

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