| Poster | Poster Session 06 Program Schedule
02/15/2024
04:00 pm - 05:15 pm
Room: Shubert Complex (Posters 1-60)
Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2
Final Abstract #30
Peripheral GDF15 Associates with Accelerated Cognitive Aging in Community-Dwelling Adults
Coty Chen, UCSF, San Francisco, United States
Emily Paolillo, UCSF, San Francisco, United States
Rowan Saloner, UCSF, San Francisco, United States
Shannon Lee, University of Florida, Gainesville, United States
Valentina Diaz, UCSF, San Francisco, United States
Miwa Tucker, UCSF, San Francisco, United States
Lana Callies, UCSF, San Francisco, United States
Savannah Hallgarth, UCSF, San Francisco, United States
Anna VandeBunte, UCSF, San Francisco, United States
Saul Villeda, UCSF, San Francisco, United States
Joel Kramer, UCSF, San Francisco, United States
Kaitlin Casaletto, UCSF, San Francisco, United States
Category: Aging
Keyword 1: aging (normal)
Keyword 2: dementia - Alzheimer's disease
Keyword 3: cognitive functioning
Objective:
Growth differentiation factor 15 (GDF15) is a protein implicated in stress response and inflammatory regulation. Previous work consistently shows peripheral GDF15 is a marker of adverse aging across organ systems, including the brain. Despite its potential as a biomarker of brain health and target for anti-aging therapeutics, the role of plasma GDF15 in human cognitive aging is poorly understood. We examined how plasma GDF15 levels related to cognition and a biomarker of neuronal axon degeneration (neurofilament light chain [NfL]) and tested whether this association was dependent on age in community-dwelling adults along the Alzheimer’s disease continuum.
Participants and Methods:
75 older adults along the Alzheimer’s disease continuum (mean [SD] age = 75.6 years [6.8]; 56% female; mean [SD] education = 17.2 years [2.5]; 77% cognitively unimpaired, 23% MCI due to AD; 49% amyloid PET positive) from the UCSF Memory and Aging Center completed neuropsychological testing and a blood draw with plasma analyzed on SomaScan (GDF15) and Simoa (NfL, pTau181). Multiple linear regressions separately examined executive functioning, memory, and plasma NfL levels as a function of plasma GDF15, age, and their interaction, controlling for sex, education, and plasma pTau181 levels.
Results:
Plasma GDF15 exhibited a medium-sized, positive correlation with age (r = 0.34, p = 0.003). GDF15 levels did not independently relate to executive functioning (b = -0.02, p = 0.851), memory (b = -0.20, p = 0.190), or NfL levels (b = 0.10, p = 0.313), when adjusting for age, sex, education, and plasma pTau181 levels. However, GDF15 moderated the effects of age on both executive functioning (b = -0.39, SE = 0.017, p = 0.001) and NfL (b = 0.26, SE = 0.006, p = 0.007) such that the detrimental effects of age on executive functioning and neuronal axon degeneration were significantly amplified in individuals with higher peripheral GDF15. In contrast, there was no significant interaction between GDF15 and age on memory (b = 0.23, SE = 0.028, p = 0.111).
Conclusions:
Older adults with higher peripheral GDF15 levels show evidence of potentiated aging effects on cognitive and axonal outcomes, independent of Alzheimer’s disease pathology levels. Our results further support the clinical relevance of GDF15 and suggest that resistance to age-related increases in GDF15 might confer resilience to cognitive and brain aging. Further examination of plasma GDF15 as a prognostic biomarker of cognitive decline and/or treatment target may be warranted.
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