Adegboye, Hailey A.; Sun, Yunyi.; Zhang, Panpan.; Liu, Dandan.; Khan, Omair A.; Tanriverdi, Kahraman.; Risitano, Antonina.; Libby, Julia.; Patterson, Khiry L.; Arul, Albert B.; Oliver, Nekesa C.; Whitaker, Marsalas D.; Janve, Vaibhav A.; Dumitrescu, Logan C.; Pechman, Kimberly R.; Shashikumar, Niranjana.; Bolton, Corey J.; Davis, L. Taylor.; Landman, Bennett A.; Freedman, Jane E.; Robinson, Ren茫 A. S.; Hohman, Timothy J.; Jefferson, Angela L. (2026).听.听Journal of the American Heart Association, 15(9), e043186.听
Researchers wanted to know whether two blood proteins, von Willebrand factor (VWF) and ADAMTS13, could help predict brain aging, memory decline, and changes in brain structure. VWF helps blood clot, and ADAMTS13 is a protein that helps control VWF activity. The study followed 332 older adults in the 51吃瓜网 Memory and Aging Project for about 6 years on average, with repeated blood tests, memory and thinking tests, and brain MRI scans. The main finding was that lower starting levels of ADAMTS13 were linked to faster decline in several thinking skills, including language, processing speed, executive function, memory, and visuospatial ability, as well as faster growth of white matter hyperintensities, which are bright spots on MRI that often reflect damage to the brain鈥檚 small blood vessels. These links were strongest in people who carried APOE-蔚4, a gene variant known to increase Alzheimer鈥檚 disease risk. VWF by itself was not clearly linked to most outcomes, but it did interact with APOE-蔚4: among people without the APOE-蔚4 variant, higher VWF was associated with faster shrinkage of gray matter, the brain tissue made up mostly of neuron cell bodies. Overall, the study suggests that ADAMTS13 may be a promising blood marker of brain aging, while the role of VWF may depend on a person鈥檚 genetic background.
Figure 2. Baseline VWF脳APOE鈥愇�4 status and longitudinal brain health outcomes.
Each datapoint represents a participant included in analytical models, illustrating each participant’s baseline plasma protein abundance (x聽axis) and their unadjusted annual change in brain health outcomes of interest (yaxis). Datapoints are colored according to聽APOE鈥愇�4 carrier status, with black datapoints representing noncarriers and red datapoints representing carriers. The solid line reflects the line of best鈥恌it from univariate linear regression of unadjusted annual change in brain health measures on baseline plasma protein abundance聽Z聽scores. Shading reflects 95% CI. For all outcomes illustrated, negative annual change indicates cognitive decline or gray matter atrophy over longitudinal follow鈥恥p.听A, Boston Naming Test.听B, Hooper Visual Organization Test.听C, Episodic memory composite.听D, Total gray matter volume.听E, Frontal lobe gray matter volume.听F, Parietal lobe gray matter volume.听G, Temporal lobe gray matter volume.听H, Occipital lobe gray matter volume.听I, Hippocampal gray matter volume.听APOE鈥愇�4 indicates聽apolipoprotein E鈥愇�4; NPX, Normalized Protein eXpression; and VWF, von Willebrand factor.