Editors' ChoiceAlzheimer’s Disease

Waving off neurodegeneration

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Science Translational Medicine  22 May 2019:
Vol. 11, Issue 493, eaax4879
DOI: 10.1126/scitranslmed.aax4879

Abstract

Gamma wave oscillations provide neuroprotection in mouse models of Alzheimer’s disease.

Neurodegenerative disorders, such as Alzheimer's disease (AD), progressively affect cognitive skills and eventually the ability to carry out the simplest tasks. Reversing the cognitive impairments is a holy grail in AD patients. In healthy brains, network communication is driven by electrical oscillating waves generated by a delicate balance between neuronal excitation and inhibition. Gamma oscillations (40 Hz) involved in learning and memory have been shown to be lost in AD.

Adaikkan et al. have reintroduced this wave with visual stimulation through 40 Hz flashing lights via a process known as gamma entrainment using sensory (GENUS) stimuli in two mouse models of AD (Tau P301S and CK-p25). Tau P301S mice have a mutated version of the Tau protein leading to neurofibrillary tangles; the second inducible mouse model produces the protein CK-p25, causing severe neurodegeneration. Overall, applying GENUS stimuli early on prevented amyloid plaque and phosphorylated tau, leading to reduced neurodegeneration in the Tau P301S and CK-p25 mouse models. In-depth probing by the researchers of how these beneficial effects arise with GENUS stimuli in these neurodegenerative mouse models showed a reduction in regulation of immune system process and antigen processing/presentation. Concurrently, there was increased vasculature development, regulation of cell morphogenesis, and intracellular signal transduction molecules.

As to whether GENUS can be translated in humans with AD, additional studies are needed. It remains to be determined whether GENUS is necessary as a preventative or maintenance treatment in AD. Excitingly, these findings indicate that alternative treatments— such as GENUS, which are noninvasive or pharmacological—might help to preserve neural and synaptic plasticity and neuronal survival in patients with AD.

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