MK‐6240 tau‐PET in an Aβ‐enriched sample from the 1946 British birth cohort

Abstract

AbstractBackgroundWe investigated imaging biomarkers of Aß and neurodegeneration in relation to tau‐PET Braak stage in a preclinical birth cohort.MethodCognitively normal individuals enrolled in Insight 46, the neuroimaging sub‐study of the MRC National Survey of Health and Development (1946 British birth cohort), were scanned on combined PET/MR with [18F]florbetapir Aß‐PET at age ∼70 years and again at ∼73 years. A sub‐sample enriched for Aß (Aß+; Centiloid> = 13, hole cerebellum reference) is currently being assessed with [18F]MK‐6240 tau‐PET at age ∼76 years. For this interim analysis, tau‐PET images (90‐110 minutes post‐injection) were co‐registered with T1‐weighted MRI. Anatomical areas were parcellated on the T1 to form Braak regions. Standard uptake value ratios (SUVRs) were calculated using an inferior cerebellar grey reference without partial volume correction. Tau‐PET positivity (Tau+) was defined using Gaussian mixture modelling in each region. Participants were assigned to Tau‐, Braak I‐II, III‐IV or V‐VI groups based on the most advanced Tau+ region. Group differences in baseline Aß (Centiloids), Aß accumulation (Centiloids/year) and hippocampal atrophy rate (%/year) were investigated with Mann‐Whitney U tests.ResultAnalysis included 80 individuals with tau‐PET data (Table 1), 45% of the sample were Aß+ by age 73. Three individuals did not conform to the Braak stage hierarchy (orange triangles, Figure 1). No Aß‐ individuals were Tau+ beyond Braak I. Figure 2 shows baseline Aß, Aß accumulation and hippocampal atrophy rates for Braak stage groups for participants who had data at all timepoints (N = 78). Tau+ individuals (in any Braak region) had significantly higher baseline Aß than Tau‐ individuals. Rate of annual Aß accumulation was higher for Braak III‐IV and Braak V‐VI compared to Tau‐ individuals. Hippocampal atrophy rate was elevated for Braak V‐VI compared to Tau‐, and Braak III‐IV was borderline significant.ConclusionIn this preliminary analysis, tau‐PET positivity beyond Braak I was restricted to individuals who were Aß+ three years prior. Participants with elevated tau aged 76 had increased Aß at age 70. Increased rates of hippocampal atrophy were occurring at least three years prior to tau scanning in individuals with advanced tau pathology. These findings will be updated as more data is acquired.