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| Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. We used resting-state magnetoencephalography to assess whether functional connectivity patterns, as an index of synaptic dysfunction, associate with cerebrospinal fluid (CSF) biomarkers (i.e., phospho-tau and amyloid beta -A?42- levels) in a sample of twelve patients with Mild Cognitive Impairment. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF phospho-tau and A?42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by phospho-tau associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the Default Mode Network and the temporal cortex. Magnetoencephalography is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. | |
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Internacional
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JCR del ISI
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Título de la revista
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The Journal of Neuroscience |
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ISSN
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0270-6474 |
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Factor de impacto JCR
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6,747 |
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