In vivo characterization of the early states of the amyloid-beta network

• Published in: Brain (London, England : 1878) Vol. 136; no. Pt 7; pp. 2239 - 2252
• Main Authors: SEPULCRE, Jorge, SABUNCU, Mert R, BECKER, Alex, SPERLING, Reisa, JOHNSON, Keith A
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2013
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Aniline Compounds; Biological and medical sciences; Brain - blood supply; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain Mapping; Carbon Isotopes; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medical sciences; Neural Pathways - blood supply; Neural Pathways - diagnostic imaging; Neural Pathways - pathology; Neurology; Original; Oxygen - blood; Positron-Emission Tomography; Thiazoles; Nervous system diseases; Alzheimer disease; early stages; Central nervous system disease; Early stage; Degenerative disease; Amyloid; Graph theory; Alzheimer's disease; Cerebral disorder; network; amyloid; Alzheimer’s disease; graph theory
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awt146

Alzheimer's disease is a neurodegenerative disease that is associated with the abnormal accumulation of amyloid-β. Much is known about regional brain atrophy in Alzheimer's disease, yet our knowledge about the network nature of Alzheimer's disease-associated amyloid-β accumulation is limited. We use stepwise connectivity analysis of Pittsburgh Compound B positron emission tomography images to reveal the network properties of amyloid-β deposits in normal elderly subjects and clinical patients with Alzheimer's disease. We found that amyloid-β accumulation in the medial temporal lobe is associated with accumulation in cortical regions such as orbitofrontal, lateral temporal and precuneus/posterior cingulate cortices in Alzheimer's disease. In normal subjects, there was a predominant association between amyloid-β deposits in the hippocampus and the midline prefrontal/orbitofrontal regions, even in those with very low amyloid-β burden. Moreover, the orbitofrontal cortex, amygdala nucleus and hippocampus exhibit hub properties in the amyloid-β network that may be critical to understanding the putative spreading mechanisms of Alzheimer's disease pathology in early stages.