Hyperspectral analysis of amyloid beta (Aβ) evolutional changes in preclinical to late‐stage Alzheimer’s disease using matched brain and retinal tissue

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive, degenerative brain disorder that leads to cognitive impairment and eventually death. It is marked by buildup of abnormal amyloid aggregates (Aβ) in the brain. This study aimed to elucidate the neuropathologic sequence and corresponding [RetiSpec] hyperspectral signals of Aβ evolutional changes in preclinical to late‐stage AD using retinal and brain samples.MethodWe used brain‐ and retina‐matched human tissue samples from the NIH Brain Bank at Johns Hopkins. Study groups included: No AD neuropathologic change with negative AD neuropathology (n = 15); Low‐level AD neuropathologic change with positive AD neuropathology (n = 15); High level AD neuropathologic change with positive AD neuropathology (n = 15). To validate retinal hyperspectral imaging (rHSI) detection of Aβ in these retinal samples, we quantified Aβ oligomers (AβOs) in human retinal tissue. Immunohistochemistry was performed. We used humanized, affinity‐matured, IgG2 mAβ selective biotinylated antibody (ACU‐193) to detect soluble AβOs in retinal and brain tissues followed by objective quantification of ACU193 retinal staining by performing annotations and data extraction using QuPath software. One‐way ANOVA and t‐tests were performed to compare between controls and AD stages.ResultWhen assessing ACU193 staining present from retinal tissue samples, we observed 29‐53% retinal tissue area positivity in controls and 15‐72% retinal tissue area positivity in the AD group. Level of AD pathology demonstrated an effect on the rHSI spectra (450‐600nm) in regions near the optic disc and the ventral periphery: intermediate AD pathology showed the strongest rHSI signature (decrease in optical transmittance) followed by high, then low AD pathology samples. Correlation of the Braak neurofibrillary tangle stage and ΔOD offered a Pearson r score of 0.79 (p = 0.004).ConclusionThis study was the first to assess and quantify AβOs in clinically, neuropathologically, and hyperspectrally characterized postmortem matched brain and retinal tissues. Progression of well‐established neuropathologically classified AD stages (e.g Braak) may correlate with retinal AβO levels measured using rHSI. Certain retina regions that share nervous tissue with the brain (optic disc, periphery) are likely more sensitive to rHSI‐mediated detection of AD pathology. Larger samples are needed to comprehensively assess and quantify retinal AβOs.