Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability

Abstract

Beta-amyloid (Aβ) deposition is one of the hallmarks of Alzheimer's disease (AD). However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [(11)C]PIB-PET in 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

“…Temporal cortex and entorhinal cortex of mice were chosen as representative region. These two regions were selected because early pathological features of AD were mainly found in the temporal lobe and in entorhinal cortex [15,16]. Consistent with previous data [17,18], we also observed that sirt3 was ubiquitous localized in the nuclear and cytoplasm.…”

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

“…9 For instance, it has repeatedly been demonstrated in PiB-PET studies that the presence of amyloid plaques is sufficient for there to be functional connectivity changes not only in the DMN, 10 but also in the SAL and ECN 32 and even between networks. 33 In the present study, we found that a lower level of CSF Aβ 1-42 was associated with decreased functional connectivity between the ventral DMN and the LN and between the ventral DMN and the anterior SAL in patients with Alzheimer disease, whereas in patients with aMCI there was stronger functional connectivity between some regions of the ventral DMN and the VSN/DAN and decreased connectivity between other regions of the ventral DMN and the VSN/ DAN. Amyloid burden in the DMN areas is a plausible explanation for the functional connectivity disruption between these RSNs; in addition, previous studies using PiB-PET amyloid imaging have demonstrated that amyloid accumulation occurs throughout the lateral frontoparietal cortex 34 and extends to the attention network, 35 affecting the functional connectivity of regions belonging to the VSN/DAN in patients with Alzheimer disease.…”

IC‐P‐033: Resting‐State Network Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta‐Analysis

“…DMN hypoconnectivity may arise as early as middle age [43,44], with decreases occurring at differing rates between sexes [45] most likely due to the differential effect of sex on AD risk [46]. Reduced DMN integrity has also been reported in cognitively normal elderly with abnormal levels of CSF amyloid or tau proteins [47], as well as PET-detectable cerebral amyloidosis [48]. These results suggest that some of the effects related to normal aging in the literature may be driven by preclinical AD.…”