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    Fundus imaging results promising for early Alzheimer’s diagnosis


    In recent years, evidence has mounted implicating amyloid beta aggregates as playing a key part in the development of Alzheimer’s, the researchers write.

    Soluble amyloid beta aggregates such as globulomers and pore-forming hollow rods appear to interact specifically with neuronal cell-membrane components.

    On one hand, pore-forming rods compromise membrane integrity, allowing for general disruption of homoeostasis. On the other hand, globulomers strongly agonise N-methyl-D-aspartate receptors, causing psychiatric changes as well as intense oxidative stress in the cytoplasm that will lead to neuronal cell-death over time.

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    The researchers argue that their technique is the first to exploit the unique optical properties of suspended particles in the size-range of around 50 to 500 nm (Rayleigh scattering itself and various magnitudes and directionalities of Mie scattering phenomenon). They point out that this size-range coincides with that of those amyloid aggregation orders that have been shown to cause the symptoms as well as the neuronal damage of Alzheimer’s disease, they write. 

    As the next step, the UMN team wanted to see if they could observe the same changes in living Alzheimer’s mice. So they used a machine vision camera and tuneable wavelength system to obtain monochromatic optical endoscope fundus images across the visible to near-infrared spectral range.

    They imaged Alzheimer's and age-matched, wild-type mice monthly from months 3 through 8 to assess changes in the fundus reflection spectrum. They fit optical changes to Rayleigh light scatter models as measures of amyloid aggregation.

    They rated as “good quality” the spectral images they obtained of the central retina. Short-wavelength reflectance from Alzheimer's mice retinas appeared to diminish over time compared with wild-type mice.

    They judged the optical changes to be consistent with an increase in Rayleigh light scattering in neural retina due to soluble amyloid beta aggregates. “The changes in light scatter showed a monotonic increase in soluble amyloid aggregates over a 6-month period, with significant build-up occurring at 7 months,” they write.

    Related: Digital Fundus Photography

    No one has ever before detected early Alzheimer's disease in a live Alzheimer's mouse using hyperspectral imagery without the use of an extraneous agent, the researchers say.

    One advantage of this technique is that it is non-invasive. The researchers were able to measure signals in live mice using a safe level of light exposure over 10 seconds.

    They anticipate that that a similar exposure duration would be used to examine light scattering changes in patients.

    “Timely diagnosis of [Alzheimer’s disease] is paramount for proper treatment and evaluation of the latter's efficacy,” the authors conclude. “We expect this technology to prove suitable for translation into a human diagnostic tool. Such developmental efforts are underway.”

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