Amyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer's disease
Amyloid-β and tau pathology in preclinical Alzheimers 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 brains functional architecture to interfere with information processing within and across neural systems, possibly contributing to the spread of pathology and ultimately resulting in dementia.