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. 2017 Aug;222(6):2877-2889.
doi: 10.1007/s00429-017-1377-3. Epub 2017 Feb 22.

Modulation of APOE and SORL1 genes on hippocampal functional connectivity in healthy young adults

Junlin Shen  1 , Wen Qin  1 , Qiang Xu  1 , Lixue Xu  1 , Jiayuan Xu  1 , Peng Zhang  1 , Huaigui Liu  1 , Bing Liu  2 , Tianzi Jiang  2 , Chunshui Yu  3
Affiliations

Modulation of APOE and SORL1 genes on hippocampal functional connectivity in healthy young adults

Junlin Shen et al. Brain Struct Funct. 2017 Aug.

Abstract

Apolipoprotein E (APOE) and sortilin-related receptor (SORL1) genes act on the same metabolic pathway and have been associated with Alzheimer's disease (AD) characterized by hippocampal impairment. Although the effects of APOE on hippocampal resting-state functional connectivity (rsFC) have been reported, the main effects of SORL1 and SORL1 × APOE interactions on hippocampal rsFC in healthy subjects remain largely unknown. Here, we systematically investigated the main effects of SORL1 rs2070045, and APOE, and their interaction effects on hippocampal rsFC in healthy young adults. The main effect of APOE showed that risk ε4 carriers had decreased positive hippocampal rsFC with the precuneus/posterior cingulate cortex and subgenual anterior cingulate cortex, and increased positive hippocampal rsFC with the sensorimotor cortex compared with non-ε4 carriers. The main effect of SORL1 showed that risk G-allele carriers had decreased positive rsFC between the hippocampus and middle temporal gyrus compared with TT carriers. No significant additive interaction was observed. Instead, significant SORL1 × APOE non-additive interaction was found in negative rsFC between the hippocampus and inferior frontal gyrus. Compared with subjects with TT genotype, SORL1 G-allele carriers had a stronger negative rsFC in APOE ε4 carriers, but a weaker negative rsFC in APOE non-ε4 carriers. These findings suggest that SORL1 and APOE genes modulate different hippocampal rsFCs and have a complex interaction. The SORL1- and APOE-dependent hippocampal connectivity changes may at least partly account for their association with AD.

Keywords: APOE; Functional connectivity; Hippocampus; SNPs; SORL1; fMRI.

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Figures

Fig. 1
Fig. 1
rsFC patterns of hippocampus. a Left hippocampus; and b right hippocampus. Positive (warm color) and negative (Cold color) correlations are projected to structural images. Color scales present T value of one-sample t test
Fig. 2
Fig. 2
Main effect of SORL1 on left hippocampal positive connectivity. Hip hippocampus, L left, MTG middle temporal gyrus, R right
Fig. 3
Fig. 3
Main effect of APOE on hippocampal positive connectivity. Hip hippocampus, L left, PCC posterior cingulate cortex, Pcu precuneus, R right, sACC subgenual anterior cingulate cortex, SMC sensorimotor cortex
Fig. 4
Fig. 4
Non-additive interaction of SORL1 and APOE on the right hippocampal negative connectivity. Hip hippocampus, IFG inferior frontal gyrus, L left, R right
See this image and copyright information in PMC

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References

    1. Agosta F, Rocca MA, Pagani E, Absinta M, Magnani G, Marcone A, Falautano M, Comi G, Gorno-Tempini ML, Filippi M. Sensorimotor network rewiring in mild cognitive impairment and Alzheimer’s disease. Hum Brain Mapp. 2010;31:515–525. - PMC - PubMed
    1. Albers MW, Gilmore GC, Kaye J, Murphy C, Wingfield A, Bennett DA, Boxer AL, Buchman AS, Cruickshanks KJ, Devanand DP, Duffy CJ, Gall CM, Gates GA, Granholm AC, Hensch T, Holtzer R, Hyman BT, Lin FR, McKee AC, Morris JC, Petersen RC, Silbert LC, Struble RG, Trojanowski JQ, Verghese J, Wilson DA, Xu S, Zhang LI. At the interface of sensory and motor dysfunctions and Alzheimer’s disease. Alzheimers Dement. 2015;11:70–98. doi: 10.1016/j.jalz.2014.04.514. - DOI - PMC - PubMed
    1. Alexopoulos P, Guo LH, Kratzer M, Westerteicher C, Kurz A, Perneczky R. Impact of SORL1 single nucleotide polymorphisms on Alzheimer’s disease cerebrospinal fluid markers. Dement Geriatr Cogn Disord. 2011;32:164–170. doi: 10.1159/000332017. - DOI - PMC - PubMed
    1. Alexopoulos P, Richter-Schmidinger T, Horn M, Maus S, Reichel M, Sidiropoulos C, Rhein C, Lewczuk P, Doerfler A, Kornhuber J. Hippocampal volume differences between healthy young apolipoprotein E epsilon2 and epsilon4 carriers. J Alzheimers Dis. 2011;26:207–210. - PubMed
    1. Allen G, Barnard H, McColl R, Hester AL, Fields JA, Weiner MF, Ringe WK, Lipton AM, Brooker M, McDonald E, Rubin CD, Cullum CM. Reduced hippocampal functional connectivity in Alzheimer disease. Arch Neurol. 2007;64:1482–1487. doi: 10.1001/archneur.64.10.1482. - DOI - PubMed

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