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In Alzheimer's disease (AD), amyloid-β (Aβ) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of Aβ and iFC to reveal both Aβ accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and Aβ imaging in a cross-sectional sample of 90 subjects across stages of AD and healthy older adults. Global and local correspondence of Aβ and iFC were assessed within the posterior default mode network (pDMN) by within-subject voxel-wise correlations. Beginning at preclinical stages, global Aβ-iFC correspondence was positive for the whole pDMN, showing that Aβ accumulates in areas of high connectivity, and reached a plateau at prodromal stages. Starting at preclinical stages, local correspondence was negative in network centers, indicating that Aβ reduces connectivity of the pDMN as a function of local plaque concentration, and peaked at prodromal stages. Positive global correspondence suggests that Aβ accumulation progresses along iFC, with this effect starting in preclinical stages, and being constant along clinical periods. Negative local correspondence suggests detrimental effects of Aβ on iFC in network centers, starting at preclinical stages, and peaking when first symptoms appear. Data reveal a complex trajectory of Aβ and iFC correspondence, affecting both Aβ accumulation and iFC impairments.

Original publication




Journal article


Journal of Alzheimer's disease : JAD

Publication Date





763 - 773


Memory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.


Alzheimer’s Disease Neuroimaging Initiative, Brain, Neural Pathways, Humans, Alzheimer Disease, Disease Progression, Positron-Emission Tomography, Magnetic Resonance Imaging, Brain Mapping, Cross-Sectional Studies, Rest, Aged, Female, Male, Amyloid beta-Peptides, Prodromal Symptoms, Multimodal Imaging, Mental Status and Dementia Tests