Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod Mitochondria Activity Early in Experimental Alzheimer?s Disease

PURPOSE. In Alzheimer's disease, central brain neurons show evidence for early hyperac-tivity. It is unclear if this occurs in the retina, another disease target. Here, we tested for imaging biomarker manifestation of prodromal hyperactivity in rod mitochondria in vivo in experimental Alzheimer's disease.METHODS. Light-and dark-adapted 4-month-old 5xFAD and wild-type (WT) mice, both on a C57BL/6J background, were studied with optical coherence tomography (OCT). We measured the reflectivity profile shape of the inner segment ellipsoid zone (EZ) as a proxy for mitochondria distribution. Two additional indices responsive to mitochondria activity were also measured: the thickness of the external limiting membrane-retinal pigment epithelium (ELM-RPE) region and the signal magnitude of a hyporeflective band (HB) between photoreceptor tips and apical RPE. Retinal laminar thickness and visual performance were evaluated.RESULTS. In response to low energy demand (light), WT mice showed the expected elon-gation in EZ reflectivity profile shape, relatively thicker ELM-RPE, and greater HB signal. Under high energy demand (dark), the EZ reflectivity profile shape was rounder, the ELM-RPE was thinner, and the HB was reduced. These OCT biomarker patterns for light-adapted 5xFAD mice did not match those of light-adapted WT mice but rather that of dark-adapted WT mice. Dark-adapted 5xFAD and WT mice showed the same biomarker pattern. The 5xFAD mice exhibited modest nuclear layer thinning and lower-than-normal contrast sensitivity.CONCLUSIONS. Results from three OCT bioenergy biomarkers raise the novel possibility of early rod hyperactivity in vivo in a common Alzheimer's disease model.