Near infrared light decreases synaptic vulnerability to amyloid beta oligomers

Michele M Comerota,Giulio Taglialatela,Balaji Krishnan

doi:10.1038/s41598-017-15357-x

Michele M Comerota, Giulio Taglialatela + Show 1 more

Open Access

https://doi.org/10.1038/s41598-017-15357-x

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Abstract

Synaptic dysfunction due to the disrupting binding of amyloid beta (Aβ) and tau oligomers is one of the earliest impairments in Alzheimer’s Disease (AD), driving initial cognitive deficits and clinical manifestation. Consequently, there is ample consensus that preventing early synaptic dysfunction would be an effective therapeutic strategy for AD. With this goal in mind, we investigated the effect of a treatment of mice with near infrared (NIR) light on synaptic vulnerability to Aβ oligomers. We found that Aβ oligomer binding to CNS synaptosomes isolated from wild type (wt) mice treated with NIR light was significantly reduced and the resulting suppression of long term potentiation (LTP) by Aβ oligomers was prevented. Similarly, APP transgenic mice treated with NIR showed a significant reduction of endogenous Aβ at CNS synapses. We further found that these phenomena were accompanied by increased synaptic mitochondrial membrane potential in both wt and Tg2576 mice. This study provides evidence that NIR light can effectively reduce synaptic vulnerability to damaging Aβ oligomers, thus furthering NIR light therapy as a viable treatment for AD.

Highlights

Alzheimer’s disease (AD) is the most common and severe age-associated neurodegenerative disorder for which there is currently no effective therapeutic intervention
We showed that while Non- Demented with Alzheimer’s Neuropathology (NDAN) individuals displayed similar levels of soluble Aβ oligomers throughout their CNS, contrary to demented Alzheimer’s Disease (AD) patients, they had synapses that were devoid of Aβ oligomers[7]
To investigate the effects of near infrared (NIR) light on synaptic sensitivity to Aβ, we studied the ex vivo Aβ oligomer binding on isolated synaptosomes from wild type mice receiving NIR light treatment

Summary

Introduction

Alzheimer’s disease (AD) is the most common and severe age-associated neurodegenerative disorder for which there is currently no effective therapeutic intervention. We showed that while NDAN individuals displayed similar levels of soluble Aβ oligomers throughout their CNS, contrary to demented AD patients, they had synapses that were devoid of Aβ oligomers[7] This suggests the possibility that synapses of NDAN subjects are resistant to Aβ oligomers and illustrates that absence of Aβ at synapse is a key event associated with preservation of cognitive integrity. Taken together this evidence suggests that eliciting a protective mechanism resulting in synaptic resilience to binding of Aβ oligomers similar to NDAN individuals would be the most effective protection against Aβ oligomer driven toxic synaptic dysfunction. These changes were in conjunction with a retention and increase in the synaptic mitochondria health after NIR light treatment in both wt and Tg2576 mouse models

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