Plasma rejuvenation factor GDF11 associates with amyloid‐related cognitive decline in older adults across the Alzheimer’s Disease spectrum

Abstract

AbstractBackgroundThrough studies of animal heterochronic parabiosis (fusion of juvenile and older adult animal circulatory systems), growth differentiation factor 11 (GDF11) has been identified as a blood rejuvenation factor that can promote neurogenesis, vascular remodeling, and memory improvement in the presence of age‐related declines. However, it is unknown whether GDF11’s associations with cognitive and neural outcomes translate to humans. We assessed the relationship between plasma GDF11, cerebral amyloid pathology, and cognitive performance in older adults across the Alzheimer’s disease (AD) spectrum.MethodParticipants were 71 older adults from the UCSF Memory and Aging Center who ranged in age from 63 to 93 (Meanage = 79.5; Meanedu = 17.5, 66 cognitively unimpaired, 56% women, 38% amyloid PET positive) and completed blood draws with plasma analyzed on Somascan (version 4.1), neuropsychological evaluations, and amyloid PET scans (18‐AV‐45). Cognition was operationalized as a of validated tests of memory and executive function. Pearson’s correlations examined interrelationships among plasma GDF11, cognition, and amyloid PET centiloids. To determine whether plasma GDF11 moderated the effects of amyloid on cognition, linear regression examined cognition as a function of GDF11, amyloid, and their interaction, controlling for age, sex, and education.ResultHigher amyloid PET centiloids correlated with worse cognition (r = ‐0.20, p = 0.09) and lower levels of GDF11 (r = ‐0.15, p = 0.20), though relationships did not reach statistical significance. GDF11 also did not strongly univariately correlate with cognition (r = ‐0.07, p = 0.59). However, there was a significant interaction between GDF11 and amyloid PET centiloids on cognition (β = 0.55, 95% CI = 0.15, 0.95, p = 0.008) such that the negative relationship between amyloid PET centiloids and cognition was significantly in participants with higher levels of GDF11.ConclusionGDF11 is a blood‐based rejuvenation factor that supports neurogenesis and cognition in animal models and attenuates the association between higher amyloid burden and worse cognition in cognitively unimpaired older adults. These results coupled with prior findings provide translational evidence that GDF11 supports brain resilience and further examination of GDF11 as a therapeutic target for Alzheimer’s disease is warranted.