Dataset Information

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOE?4-associated Alzheimer's disease.

ABSTRACT: BACKGROUND:Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease. METHODS:Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized and compared between APOE-?4+ carriers and APOE-?4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-?4+ carriers versus APOE-?4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS:In ABCA7 rs3764650G allele carriers, APOE-?4+ carriers had lower memory scores (t (159)?=?-?4.879; P??0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283?=?4.755, P?=?0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P?=?0.00002) was correlated with the memory (??=?0.129, P?=?0.030). CONCLUSIONS:Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer's disease and refining a potential therapy.

SUBMITTER: Chang YT

PROVIDER: S-EPMC6909474 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

Chang Ya-Ting YT Hsu Shih-Wei SW Huang Shu-Hua SH Huang Chi-Wei CW Chang Wen-Neng WN Lien Chia-Yi CY Lee Jun-Jun JJ Lee Chen-Chang CC Chang Chiung-Chih CC

Alzheimer's research & therapy 20191212 1

<h4>Background</h4>Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease.<h4>Methods</h4>Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized a ...[more]

PMID: 31831047

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Project description:Objective:To investigate the impact of Alzheimer's disease (AD)-related risk gene (ATP-binding cassette A7-ABCA7 and Clusterin-CLU) on the functional connectivity pattern of default mode network (DMN) in healthy middle-age adults. Methods:A total of 147 healthy middle-aged volunteers were enrolled in this study. All subjects completed MRI scans, neuropsychological assessments, and AD-related genotyped analysis. All subjects were divided into high, middle and low risk groups according to the score of risk genotypes, which included CLU (rs11136000, rs2279590, rs9331888, and rs9331949) and ABCA7 (rs3764650 and rs4147929). The genetic effects of CLU, ABCA7, and CLU × ABCA7 on DMN functional connectivity pattern were further explored. Moreover, the genetic effect of Apolipoprotein ?4 (APOE?4) was also considered. Finally, correlation analysis was performed between the signals of brain regions with genetic effect and neuropsychological test scores. Results:Compared with the low-risk group, the high-risk group of CLU showed decreased functional connectivity in posterior cingulate cortex (PCC) and the left middle frontal cortex (P < 0.05, GRF correction). As for the interaction between the CLU and ABCA7, all the subjects were divided into high, middle, and low risk group; the middle-risk group was divided into CLU and ABCA7-dominated middle-risk group. The function connectivity pattern of DMN among the three or four groups were distributed in the bilateral medial prefrontal cortex (MPFC) and bilateral superior frontal gyrus (SFG) (P < 0.05, GRF correction). When APOE?4 carriers were excluded, the CLU-predominant middle-risk group displayed the decreased functional connectivity in MPFC when compared with the low-risk group, while ABCA7-prodominant middle-risk group displayed decreased functional connectivity in cuneus when compared with the high-risk group (all P < 0.05, GRF correction). The z values of left middle frontal cortex were positively correlated with the scores of Serial Dotting Test (SDT) in high-risk group of CLU, while z values of MPFC and cuneus were positively correlated to the scores of Montreal Cognitive Assessment (MoCA) in low-risk group of three or four groups. Conclusion:The functional connectivity of MPFC-PCC might be modulated by the interaction of CLU and ABCA7. Moreover, APOE?4 might be interacted with ABCA7 and CLU modulation in the middle-aged carriers.

Project description:Default mode network (DMN) is a functional brain network with a unique neural activity pattern that shows high activity in resting states but low activity in task states. This unique pattern has been proved to relate with higher cognitions such as learning, memory and decision-making. But neural mechanisms of interactions between the default network and the task-related network are still poorly understood. In this paper, a theoretical model of coupling the DMN and working memory network (WMN) is proposed. The WMN and DMN both consist of excitatory and inhibitory neurons connected by AMPA, NMDA, GABA synapses, and are coupled with each other only by excitatory synapses. This model is implemented to demonstrate dynamical processes in a working memory task containing encoding, maintenance and retrieval phases. Simulated results have shown that: (1) AMPA channels could produce significant synchronous oscillations in population neurons, which is beneficial to change oscillation patterns in the WMN and DMN. (2) Different NMDA conductance between the networks could generate multiple neural activity modes in the whole network, which may be an important mechanism to switch states of the networks between three different phases of working memory. (3) The number of sequentially memorized stimuli was related to the energy consumption determined by the network's internal parameters, and the DMN contributed to a more stable working memory process. (4) Finally, this model demonstrated that, in three phases of working memory, different memory phases corresponded to different functional connections between the DMN and WMN. Coupling strengths that measured these functional connections differed in terms of phase synchronization. Phase synchronization characteristics of the contained energy were consistent with the observations of negative and positive correlations between the WMN and DMN reported in referenced fMRI experiments. The results suggested that the coupled interaction between the WMN and DMN played important roles in working memory.Supplementary informationThe online version contains supplementary material available at 10.1007/s11571-021-09674-1.

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Dataset Information

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOE?4-associated Alzheimer's disease.

Publications

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

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