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 hyperactivity. 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 elongation 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.

Dried blood spots are a valid alternative to venipuncture for COVID-19 antibody testing.

BACKGROUND: Serologic analysis is an important tool towards assessing the humoral response to COVID-19 infection and vaccination. Numerous serologic tests and platforms are currently available to support this line of testing. Two broad antibody testing categories are point-of-care lateral flow immunoassays and semi-quantitative immunoassays performed in clinical laboratories, which typically require blood collected from a finger-stick and a standard venipuncture blood draw, respectively. This study evaluated the use of dried blood spot (DBS) collections as a sample source for COVID-19 antibody testing using an automated clinical laboratory test system. METHODS: Two hundred and ninety-four participants in the BLAST COVID-19 seroprevalence study (NCT04349202) were recruited at the time of a scheduled blood draw to have an additional sample taken via finger stick as a DBS collection. Using the EUROIMMUN assay to assess SARS-CoV-2 anti-spike IgG status, DBS specimens were tested on 7, 14, 21, and 28 days post- collection and compared to the reference serum sample obtained from a blood draw for the BLAST COVID-19 study. RESULTS: SARS-CoV-2 anti-spike IgG status from DBS collections demonstrated high concordance with serum across all time points (7-28 days). However, the semi-quantitative value from DBS collections was lower on average than that from serum, resulting in increased uncertainty around the equivocal-to-positive analytical decision point. CONCLUSIONS: DBS collections can be substituted for venipuncture when assaying for COVID-19 IgG antibody, with samples being stable for at least 28 days at room temperature. Finger-stick sampling can therefore be advantageous for testing large populations for SARS-CoV-2 antibodies without the need for phlebotomists or immediate processing of samples. We have high confidence in serostaus determination from DBS collections, although the reduced semi-quantitative value may cause some low-level positives to fall into the equivocal or even negative range.