Open AccessAmyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease
Author(s) -
Edmarie Guzmán-Vélez,
Ibai Diez,
Dorothée Schoemaker,
Enmanuelle PardillaDelgado,
Clara VilaCastelar,
Joshua T FoxFuller,
Ana Baena,
Reisa A. Sperling,
Keith A. Johnson,
Francisco Lopera,
Jorge Sepulcre,
Yakeel T. Quiroz
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2113641119
Subject(s) - neuroscience , presenilin , dementia , disease , alzheimer's disease , neuroimaging , psychology , amyloid (mycology) , cognition , medicine , pathology
SIGNIFICANCE Amyloid-β and tau, hallmark pathologies of Alzheimer’s disease (AD), are hypothesized to spread through brain functional networks that are critical for neural communication. Using high-resolution network analyses and positron emission tomography, we showed that greater tau burden was related to functional dysconnectivity of regions associated with memory function and increased connectivity of structures that are important for integrating information in cognitively unimpaired Presenilin-1 E280A carriers, who will develop early-onset AD dementia. These findings enlighten how brain pathology relates to distinct patterns of functional connectivity in regions that are essential for memory and information processing. Elucidating how brain pathology alters functional connections before individuals experience cognitive impairment could help detect AD early and predict disease progression and dementia risk.