ABSTRACT
Amyloid-β and tau pathology in preclinical Alzheimer’s disease (AD) are hypothesized to propagate through brain networks that are critical for neural communication. We used high-resolution graph-based network analyses to test whether in vivo amyloid-β and tau burden related to segregation and integration of functional brain connections, and their association with memory, in cognitively-unimpaired Presenilin-1 E280A carriers who will develop early-onset AD dementia. Greater tau burden predicted weaker functional segregation and integration of the precuneus with other densely connected regions like the insula and entorhinal cortex, a site of early tau accumulation that is critical for memory. We also observed greater segregation and integration in the striatum and multimodal integrated networks that harbor amyloid-β early. Findings enlighten our understanding of how AD-related pathology distinctly alter the brain’s functional architecture to interfere with information processing within and across neural systems, possibly contributing to the spread of pathology and ultimately resulting in dementia.
Competing Interest Statement
Dr. Lopera was supported by an Anonymous Foundation, and the Administrative Department of Science, Technology and Innovation. He is the co-principal investigator of the Alzheimers Prevention Initiative (API) Autosomal Dominant Alzheimers disease Trial, which is supported by NIA, philanthropy, Genentech, and Roche. Dr. Sperling receives research support from Eli Lilly (clinical trial) and the Alzheimers Association. She is a site principal investigator or co-investigator for Avid, Bristol-Myers Squibb, Pfizer, and Janssen Alzheimer Immunotherapy clinical trials. She receives travel funding and honoraria from AC Immune, Janssen, and Roche. She consults for Biogen, Roche, AC Immune, Eisai, Takeda, Neurocentria, and Janssen. Spouse consults for Novartis, AC Immune and Janssen. Dr. Johnson has provided consulting services for Novartis, Biogen, and Eli Lilly, received support from a joint NIH-Lilly-sponsored clinical trial (A4 Study - U19AG10483), and received research support from the Alzheimers Association and Marr Foundation.