Evaluation of low-level light therapy assists Alzheimer's research

25 Feb 2025

Chinese project develops optical imaging technique to monitor plaque aggregation.

Non-linear imaging: plaques observed

The non-linear technique, described in Biomedical Optics Express, could offer a way to monitor the effect of low-level light therapy on the development of Alzheimer's disease (AD).

Low-level light therapy, also called photobiomodulation (PBM), has emerged as a promising approach to Alzheimer's treatment, commented the project, but the exact scope of its therapeutic value has not yet been assessed.

"The therapeutic effects of PBM on AD are thought to primarily arise from its ability to promote the regeneration of neuronal cells, and reduce neuronal loss associated with the accumulation of beta amyloid plaques," noted the team in its paper.

"However, it remains unclear whether PBM can directly reduce beta amyloid plaque levels in neuronal cells."

Previous research into how best to monitor the effects of Alzheimer's treatment with optical techniques has included a number of fluorescence-based methods, such as the 2017 project studying how the disease manifests in the retina, and a 2021 approach combining hyperspectral imaging and OCT.

But the presence of the organic molecules used as fluorescent markers is known to interfere with other proteins and biomolecules, potentially creating toxicity or disrupting the overall effects of the therapy.

PBM meanwhile has been applied to a range of therapeutic procedures, such as the recovery from burn wounds and mouth cancers, thanks to the effects of low-level incident light on specific proteins involved in the healing process.

Capturing the dynamics of plaque aggregation

The new project aimed to study whether label-free two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging could collectively be effective tools for monitoring beta amyloid plaque aggregation, a proposition tested using 3D cell cultures capable of secreting beta amyloid plaque as models for Alzheimer's disease.

PBM treatment involved use of a custom diode laser to deliver 808, 1064, 1210 and 1470 nanometer irradiation. Varying light doses of 3, 10 and 30 joules per square centimeter were applied to the cell models for seven days. Non-linear label-free imaging via TPEF and SHG excited by femtosecond pulses of 680 to 1300-nanometer light was then carried out, with the emission autofluorescence and harmonic generation signals generated by the plaque molecules recorded.

These nonlinear optical images revealed that PBM, particularly with the 808 nanometer laser, significantly reduced beta amyloid aggregation. This wavelength-dependent response suggests that specific near-IR wavelengths are more effective in mitigating aggregation, perhaps due to their differential interaction with cellular components.

"Compared to single-photon excited fluorescence imaging,nonlinear optical imaging offers deeper tissue penetration and higher spatial resolution, crucial for accurately capturing the dynamics of beta amyloid plaque aggregation in a 3D cellular environment," said the project.