A blood‐based diagnostic for Alzheimer’s disease using spectral microscopy of immuno‐enriched Aβ from frozen PBMCs

In Alzheimer’s disease (AD), toxic Aβ peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. As immune cells contact these pathological brain materials, they may act as “sentinels” that are detectable once they return to the circulation. Previously, we have demonstrated that leukocytes, when stained with an amyloid sensitive probe, K114 (Tocris Bioscience), display distinct spectral changes in subjects with AD and mild cognitive impairment (MCI) (Black et al. 2022). Here we extend this work by introducing an enhanced method that combines the specificity of immunocapture of Aβ peptides together with spectral interrogation to reveal their amyloid character from easily obtainable frozen peripheral blood mononuclear cells (PBMCs).