Optical coherence tomography (OCT) metrics and ptau isomer biomarkers in presymptomatic Alzheimer’s disease (Pre-AD)

Abstract

Purpose : Plasma tau levels correlate with neurodegeneration and cognitive decline and can differentiate AD from other neurodegenerative diseases (Mol Neurodegener. 2023;18(1):18). We explored the association between plasma tau and neuroaxonal OCT metrics in cognitively healthy (CH) pre-AD subjects.

Methods : A total of 16 subjects with a CSF Aβ42/Tau ratio ≥ 2.7 were defined to have a normal Aβ42/Tau (NATs) ratio, and those below this cut-point were defined to have a pathologic Aβ42/Tau (PATs) ratio with pre-AD (PLOS One 2013). All subjects were imaged on SD-Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) using the 6x6 mm OCT volume scans (ART 5, 20○x20○, lines 97) centered on the optic nerve; 1mm, 3.3mm diameter rings around the optic disc and an ETDRS grid of 1mm, 3mm, 6mm diameter rings around the macula were used for thickness measurement. Plasma ptau 217, ptau 181, and total tau were measured by Meso Scale Discovery (MSD, Rockville, MD) electrochemiluminescence assays. The partial correlations test was used to account for the correlation between the two eyes in a subject.

Results : Thirty-two eyes of 16 subjects were classified as 24 CH-PATs eyes and 8 CH-NATs eyes. In the CH-PATs, plasma ptau 217/total tau levels correlated with thinning of IPL-superior (r= -0.427; p<0.006), but plasma ptau 181/total tau levels did not. Total tau levels in CH-PATs correlated with thinning of GCL- center (r = -0.388; p<0.034)), and IPL-center (r = -0.485; p<0.006) sectors. The RNFL thickness did not correlate with the tau levels.

Conclusions : In this retrospective study, plasma ptau 217/total tau, not ptau 181/total, correlated with the superior IPL in CH-PAT subjects. Total tau in CH-PATs correlated with central GCL and central IPL thinning. Therefore, superior IPL thinning appears to be an earlier surrogate marker of neurodegeneration in pre-AD than GCL and RNFL.

This abstract was presented at the 2024 ARVO Imaging in the Eye Conference, held in Seattle, WA, May 4, 2024.