Amyloid deposition is associated with impaired default network function in older persons without dementia

By R. Sperling, Peter S. LaViolette, K. O'Keefe, J. O’Brien, Dorene M. Rentz, M. Pihlajamäki, G. Marshall, Bradley T. Hyman, D. Selkoe, Trey Hedden and 3 more. Neuron, 2009

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Summary Alzheimer's disease (AD) has been associated with functional alterations in a distributed network of brain regions linked to memory function, with a recent focus on the cortical regions collectively known as the default network. Posterior components of the default network, including the precuneus and posterior cingulate, are particularly vulnerable to early deposition of amyloid β-protein, one of the hallmark pathologies of AD. In this study, we use in vivo amyloid imaging to demonstrate that high levels of amyloid deposition are associated with aberrant default network functional magnetic resonance imaging (fMRI) activity in asymptomatic and minimally impaired older individuals, similar to the pattern of dysfunction reported in AD patients. These findings suggest that amyloid pathology is linked to neural dysfunction in brain regions supporting memory function and provide support for the hypothesis that cognitively intact older individuals with evidence of amyloid pathology may be in early stages of AD.

Subfields: Neurology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/17dc7bd24d8fa8e146fc049a39b444e47591345e

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Citations in the corpus

The Brain’s Default Network and its Adaptive Role in Internal Mentation (2011, background): “…within the MTL subsystem are also reliably engaged when individuals retrieve contextual associations (Bar 2007), semantic and conceptual knowledge (Binder and others 1999, 2009), and spatial information (i.e., when navigating a familiar environment; Spiers and Maguire 2006; Vann and others 2009).”
Amyloid-β Induced Neuronal Dysfunction in Alzheimer’s Disease: From Synapses toward Neural Networks (2010, background): “For example, hypometabolic regions in the parietal cortex show aberrant increases in neuronal activity during memory encodin”
Can structure predict function in the human brain? (2010, positive): “Importantly, areas of increased amyloid deposition in healthy and potentially pre-MCI elderly individuals exhibited abnormal taskrelated BOLD signal in DMN regions (Sperling et al., 2009).”
Neuronal activity regulates the regional vulnerability to amyloid-β deposition (2011, background): “as well as cognitively normal adults who harbor appreciable amyloid burde”
Brain imaging in Alzheimer disease. (2012, background): “…on PET imaging have shown evidence of disrupted default network activity during memory tasks and at rest (Hedden et al. 2009; Sheline et al. 2009; Sperling et al. 2009), suggesting these markers may be particularly useful to track response to antiamyloid therapies in preclinical trials. fMRI,…”
Amyloid Precursor Protein Processing and Alzheimer’s Disease (2011, background): “These are also the areas (posterior cingulate and parietal cortex) with the earliest Aβ accumulation (Sperling et al. 2009).”