Frequency Specific Effects of ApoE ε4 Allele on Resting-State Networks in Nondemented Elders

Abstract

We applied resting-state functional magnetic resonance imaging (fMRI) to examine the Apolipoprotein E (ApoE) ε4 allele effects on functional connectivity of the default mode network (DMN) and the salience network (SN). Considering the frequency specific effects of functional connectivity, we decomposed the brain network time courses into two bands: 0.01–0.027 Hz and 0.027–0.08 Hz. All scans were acquired by the Alzheimer's Disease Neuroscience Initiative (ADNI). Thirty-two nondemented subjects were divided into two groups based on the presence (n = 16) or absence (n = 16) of the ApoE ε4 allele. We explored the frequency specific effects of ApoE ε4 allele on the default mode network (DMN) and the salience network (SN) functional connectivity. Compared to ε4 noncarriers, the DMN functional connectivity of ε4 carriers was significantly decreased while the SN functional connectivity of ε4 carriers was significantly increased. Many functional connectivities showed significant differences at the lower frequency band of 0.01–0.027 Hz or the higher frequency band of 0.027–0.08 Hz instead of the typical range of 0.01–0.08 Hz. The results indicated a frequency dependent effect of resting-state signals when investigating RSNs functional connectivity.

APOE ε4 status in healthy older African Americans is associated with deficits in pattern separation and hippocampal hyperactivation

“…Notably, in our study, no group differences were observed on broad measures of cognitive intactness, suggesting that the presence of an APOE ε4 allele disrupts episodic memory in older adults who are otherwise cognitively healthy. These results add to the growing body of evidence on the association between APOE ε4 and episodic memory in the elderly (Caselli et al, 2011; Liang et al, 2017; Mayeux et al, 2001; Nilsson et al, 2006). Moreover, the mnemonic discrimination paradigm is particularly sensitive to the core constructs taxed by MTL pathology, compared to other episodic memory tasks, such as RAVLT, as demonstrated by previous research showing strong correlations between behavioral discrimination with both preclinical hippocampal hyperactivity and perforant path integrity (Yassa et al, 2010, 2011b).…”

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan

“…In general, APOE 4 and its association with different measurable clinical variables such as dementia severity [84], neuropsychological scores [85], pathology burdens [86], cortical morphometry [5], morphometric-MRI [87,88], functional-MRI [89–91], electroencephalographic (EEG) [92,93] and magnetoencephalographic (MEG) signals [94], evoked potentials (EPs) changes [95,96], and other methods [97] has been investigated much more extensively than APOE 2 [98–100]. In fact, studies focusing on APOE 2 and its association to different clinical and subclinical parameters and possible molecular mechanisms of brain protection have been historically, less numerous than investigations comparing APOE 4 vs. APOE 3 for example.…”

Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease

“…On the one hand, decreased DMN connectivity was detected in the PCC/Pcu and orbital frontal cortex [47,48]; on the other hand, increased DMN connectivity was found in MTL and PFC structures [47,48]. Almost overlapping results were observed in elderly APOE ε 4 carriers [49–53], even before the onset of brain amyloid accumulation processes [20,48]. …”

“…Young adult APOE ε 4 carriers showed increased functional connectivity in the sensorimotor network [34] and decreased connectivity between the auditory network and several other brain regions in the frontal, temporal, and parietal cortices, as well as in the basal ganglia [43]. Furthermore, elderly APOE ε 4 carriers displayed increased connectivity in the salience network, which is comprised of the dorsal anterior cingulate cortex (dACC), the frontoinsular cortices and subcortical and limbic regions [49,53]. Again, a number of additional brain regions, not typically involved in AD, such as the dorsal occipital cortex and the frontoparietal operculum, showed differences in functional connectivity in CN APOE ε 4 carriers compared to non-carriers [50].…”