Paper
Introduction & Objective: Diabetes increases risk of dementia, yet underlying neuropathology is unclear. While DR is associated with AD in adults with type 2 diabetes, less is known in young people with T1D. This study assessed plasma phosphorylated tau-181 (pTau181), a preclinical biomarker of AD, in young adults with T1D, by DR status. Methods: Plasma pTau181 (pg/mL) was quantified in participants with T1D using samples from the SEARCH for Diabetes in Youth study Colorado site. Samples were taken from the baseline visit, at which time no DR was present (≤2 years of T1D duration; mean age 11 [4.2] years), and a follow-up (F/U) visit in young adulthood (mean age 21 [4.6] years). DR was assessed via fundus photography at F/U and defined as any DR present. Changes in levels of pTau181 over time were assessed with paired Wilcoxon signed-rank test and compared by DR status via Mann-Whitney U test. Results: 45 participants were included (DR at F/U, n=18; No DR at F/U, n=27). pTau181 significantly increased over time in all participants (median [IQR]; 16.64 [12.60-23.67] to 109.60 [91.25-128.90], p<0.001) but there were no significant differences by DR status. Conclusion: Young adults with T1D show increasing burden of preclinical markers of AD neuropathology over time, unrelated to DR. Studies are underway to investigate the implications of these findings on cognitive function and future risk of AD in T1D. Disclosure M.E. Pauley: None. C. Coughlan: None. A. Bellatorre: None. J.K. Snell-Bergeon: None. D. Dabelea: None. A. Shapiro: None. Funding NIH NIDDK and CDC (1R01DK127208-01, 1UC4DK108173); NIH NIDDK (T325T32DK063687); DiabDocs Physician-Scientist Career Development Award: NIH NIDDK (K12DK133995) & The Leona M. and Harry B. Helmsley Charitable Trust to Stanford University (2305-06041)