Altered structural network organization in cognitively normal individuals with amyloid pathology

Area of Science:

• Neuroscience
• Neuroimaging
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) involves disrupted structural network topology, even in early stages.
• Amyloid accumulation, a key AD marker, precedes symptoms by decades, but its early effects on brain connectivity are unclear.

Purpose of the Study:

• To investigate global and local network changes in cognitively healthy individuals with and without amyloid-beta (Aβ) pathology.
• To determine if Aβ pathology impacts brain network organization before cortical thinning is evident.

Main Methods:

• Analysis of structural correlation matrices from magnetic resonance imaging cortical thickness data in 299 individuals.
• Assessment of global network efficiency and modularity, and local network organization (modules and hubs).
• Categorization of participants based on cerebrospinal fluid Aβ42/Aβ40 levels to identify Aβ pathology.

Main Results:

• Individuals with Aβ pathology showed decreased global network efficiency and modularity.
• Aβ-positive individuals exhibited fewer and more disorganized modules, along with a loss of network hubs.
• No significant regional cortical atrophy was detected in the Aβ-positive group, despite network alterations.

Conclusions:

• Structural network topology changes occur during the presymptomatic (preclinical) stage of Alzheimer's disease.
• These network alterations, including hub loss, may precede detectable cortical thinning in AD.
• Amyloid-beta pathology significantly impacts brain network organization even in the earliest, preclinical stages of AD.