Regional distribution of tau pathology in cognitively unimpaired, genetically identical twins

Abstract

AbstractBackgroundLimited information is available on the genetic and environmental contributions to early AD pathology. Within a sample of cognitively unimpaired genetically identical older twins we aimed to assess 1) effects of amyloid‐ß pathology on [18F]flortaucipir (tau) binding and 2) spatial similarities in tau patterns within twin pairs.MethodTo date, ten twin pairs (i.e. twenty twins) from the on‐going EMIF‐AD PreclinAD study underwent dynamic (0‐30min and 80‐100min) [18F]flortaucipir PET. Two twin pairs were concordant amyloid‐ß positive, four twin pairs concordant amyloid‐ß negative and four twin pairs amyloid‐ß discordant (i.e. one twin positive and co‐twin negative) based on [18F]flutemetamol visual read. [18F]flortaucipir binding potential (BPND) images were generated using receptor parametric mapping (reference region: cerebellar gray matter). First, we compared [18F]flortaucipir BPND in an early (entorhinal), intermediate (limbic) and late (neocortical) stage tau pathology region between amyloid‐ß positive and negative twins using generalized estimated equation correcting for twin dependency. Next, we examined spatial tau pattern similarities within twin pairs by correlating (Spearman) [18F]flortaucipir BPND across 46 ROIs from the Hammers template between each twin and their co‐twin for each true twin pair. Correlations were also performed for all non‐twin “random” pairs. Correlation coefficients within true twin pairs were compared to the correlation coefficients within random pairs, correcting for age and twin amyloid‐ß status.ResultsAmyloid‐ß positive twins showed higher [18F]flortaucipir BPND in entorhinal (p=0.01) and limbic (p=0.04) regions(Table‐1). Fig‐1 shows representative [18F]flortaucipir images of an amyloid‐ß concordant positive, concordant negative and discordant pair, with regional similarities observed in amyloid‐ß concordant pairs as well as dissimilarities in amyloid‐ß discordant pairs (Fig‐1;Fig‐2). Between‐twin correlations across regional [18F]flortaucipir BPND, to assess spatial tau pattern similarities, were higher for true twin pairs (r=0.71±0.17) compared to random pairs (r=0.45±0.23) (p=0.002)(Table‐2).ConclusionIn line with previous studies, amyloid‐ß positive cognitively unimpaired twins showed higher tau deposition in early and intermediate tau stage regions. Furthermore, we observed higher spatial tau pattern similarities within true twin pairs compared to random pairs, suggesting a moderate genetic contribution to mechanisms underlying tau spread. With the upcoming larger sample we aim to further assess genetic and environmental contributions to early AD pathology.