A Multi-Omics Study of Cognitive Resilience to Alzheimer's Disease

Wang, E.; Xie, B.; Wang, M.; Fu, Y.; Wang, X.; Li, Y.; Xu, P.; Liu, H.; Ho, L.; Tu, Z.; Mobbs, C.; Gaiteri, C.; Ehrlich, M. E.; Bennett, D. A.; Haroutunian, V.; Peng, J.; Zhang, B.

doi:10.64898/2026.09.02.746746

bioRxiv · 10.64898/2026.09.02.746746

A Multi-Omics Study of Cognitive Resilience to Alzheimer's Disease

Wang, E.·Xie, B.·Wang, M.·Fu, Y.·Wang, X.·Li, Y.·Xu, P.·Liu, H.·Ho, L.·Tu, Z.·Mobbs, C.·Gaiteri, C.·Ehrlich, M. E.·Bennett, D. A.·Haroutunian, V.·Peng, J.·Zhang, B.

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Abstract

Alzheimers disease (AD) is the most severe form of dementia. While significant efforts have been made to identify AD risk factors and develop therapeutics, much less attention has been given to neurobiological factors and molecular signatures associated with cognitive resilience. Substantial evidence suggests that modifiable factors, such as physical and mental activity, may contribute to cognitive reserve and resilience. To this end, we developed a resilient cohort of paired genetics, transcriptomics and proteomics data from the prefrontal cortex of 282 cognitively normal older adults. We conducted extensive preprocessing and rigorous quality control (QC), including QC on sequence metrics and sample matching across multiomics. This cohort can be leveraged for identification of molecular signatures of cognitive resilience to AD and is freely shared with the research community.

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Wang, E., Xie, B., Wang, M., Fu, Y., Wang, X., Li, Y., Xu, P., Liu, H., Ho, L., Tu, Z., Mobbs, C., Gaiteri, C., Ehrlich, M. E., Bennett, D. A., Haroutunian, V., Peng, J., Zhang, B.. 2026-09-06. A Multi-Omics Study of Cognitive Resilience to Alzheimer's Disease. https://doi.org/10.64898/2026.09.02.746746

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