Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study
Allison L. B. Shapiro,
Christina Coughlan,
Brianne M. Bettcher,
Meghan E. Pauley,
Jeongchul Kim,
Petter Bjornstad,
Benjamin Rajic,
Jennifer Truong,
Christopher Bell,
Ye Ji Choi,
Keenan A. Walker,
Huntington Potter,
Angela D. Liese,
Dana Dabelea,
Christopher T. Whitlow
Affiliations
Allison L. B. Shapiro
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado at Anschutz (CU-Anschutz), Aurora, CO 80045, USA
Christina Coughlan
University of Colorado Alzheimer’s and Cognition Center, CU-Anschutz, Aurora, CO 80045, USA
Brianne M. Bettcher
Department of Neurology, SOM, CU-Anschutz, Aurora, CO 80045, USA
Meghan E. Pauley
Barbara Davis Center for Diabetes, CU-Anschutz, Aurora, CO 80045, USA
Jeongchul Kim
Radiology Informatics and Image Processing Laboratory, Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Petter Bjornstad
Section of Endocrinology, Department of Pediatrics, School of Medicine (SOM), CU-Anschutz, Aurora, CO 80045, USA
Benjamin Rajic
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado at Anschutz (CU-Anschutz), Aurora, CO 80045, USA
Jennifer Truong
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado at Anschutz (CU-Anschutz), Aurora, CO 80045, USA
Christopher Bell
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado at Anschutz (CU-Anschutz), Aurora, CO 80045, USA
Ye Ji Choi
Section of Endocrinology, Department of Pediatrics, School of Medicine (SOM), CU-Anschutz, Aurora, CO 80045, USA
Keenan A. Walker
Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD 20814, USA
Huntington Potter
University of Colorado Alzheimer’s and Cognition Center, CU-Anschutz, Aurora, CO 80045, USA
Angela D. Liese
Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
Dana Dabelea
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado at Anschutz (CU-Anschutz), Aurora, CO 80045, USA
Christopher T. Whitlow
Radiology Informatics and Image Processing Laboratory, Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p p p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.
