Skip to main content
ENDO 2026 Main banner

Diabetes and Vascular Disease

MON-648 - Biomarkers of Neurodegeneration and Neuroinflammation in Type 1 Diabetes: Adolescents/Young Adults vs. Midlife Adults

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor


Background: Type 1 diabetes (T1D) is linked to deleterious neurologic impacts across the lifespan, including poorer cognitive function in youth and risk of neurodegenerative disorders and dementias in older age. However, the underlying neuropathology and its emergence during the life span is not fully understood. Quantification of plasma biomarkers of neurodegeneration and neuroinflammation holds promise in risk prediction, diagnosis, and monitoring of various neurologic aberrations, but there has been limited study into how these biomarker levels trend across the lifespan. This represents a critical gap in understanding, given the neurodevelopmental maturation that occurs across adolescence and young adulthood. Further, few studies have examined these biomarkers in diabetes. This study aimed to compare plasma levels of biomarkers of neurodegeneration and neuroinflammation in adolescents/young adults (AYA) and midlife adults with T1D.

Methods: Plasma samples from the SEARCH for Diabetes in Youth (SEARCH) and the Coronary Artery Calcification in Type 1 Diabetes (CACTI) studies were included. Biomarker levels (phosphorylated Tau-181 [pTau-181], total tau [Tau], amyloid β-42/amyloid β-40 [Aβ42/Aβ40], glial fibrillary acidic protein [GFAP], and neurofilament light chain [NfL]) were quantified via Simoa (Quanterix) and compared with Mann Whitney tests. Multivariable linear regression was used to test the association between age group (AYA vs. midlife adult) and log-transformed biomarker levels, adjusted for sex, race, HbA1c, age at T1D diagnosis, kidney function (estimated glomerular filtration rate; eGFR), and severity of diabetic retinopathy (DR).

Results: A total of 169 participant samples were included in the current analysis, comprising 79 AYA (age 21±4 yrs, 49% female, 52% White, age at T1D diagnosis 10±4 yrs, HbA1c 9.0±2.0%, eGFR 130±17 mL/min/1.73 m², 99% with none/mild DR and 1% with moderate DR) and 90 midlife adults (age 52±9 yrs, 58% female, 96% White, age at T1D diagnosis 15±8 yrs, HbA1c 7.6±1.0%, eGFR 85±21 mL/min/1.73 m², 52% with none/mild DR and 48% with moderate/severe DR). AYA had higher median pTau-181 (112.7 vs. 17.9 pg/mL), Tau (23.1 vs. 3.4 pg/mL), and Aβ42/Aβ40 (0.05 vs. 0.04 pg/mL), and lower GFAP (68.2 vs. 110.8 pg/mL) and NfL (7.6 vs. 10.7 pg/mL) (p < 0.01 for all). Independent of covariates, AYA was associated with higher pTau-181 (estimate [95% CI]; 0.99 [0.89, 1.1]), Tau (0.96 [0.83, 1.1]), NfL (0.12 [0.02, 0.23]), and Aβ42/Aβ40 (0.09 [0.004, 0.17]), compared to midlife adults (p < 0.05 for all).

Conclusions: Unexpectedly, compared to midlife adults, AYA was associated with higher plasma levels of pTau-181 and Tau. Further study is needed to determine if these findings reflect physiology that is unique to adolescence and young adulthood, such as neurodevelopmental maturation. These results highlight the need for age- and disease-specific references.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*