Abstract
The apolipoprotein E (APOE) ε4 allele associates with accelerating the conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD), whereas the protectiveAPOEε2 allele appears to be against the disease. Moreover, entorhinal cortex (ERC) is one of the earliest brain regions of AD pathology that disrupts the formation of episodic memory. To investigate the effects of APOE ε2 and ε4alleles on functional connectivity (FC) of ERC and cognition in aMCI. Methods The FC analyses of ERC were performed in 83 aMCI (9 ε2-carrier, 44 ε3ε3, and 30 ε4-carrier) and 88 healthy controls (HC, 15 ε2-carrier, 40 ε3ε3, and 33 ε4-carrier). Multiple linear regression model was performed between the altered ERC connectivities and cognition. In the ERC network, aMCI with ε4-carriers showed decreased FC in the bilateral middle temporal gyrus (MTG), right precuneus, and right precentral gyrus (PreCG), while ε2-carriers showed increased FC in these regions (except the right PreCG) compared to HC. The altered FC between ERC and right MTG correlated with episodic memory performance in aMCI carried ε2 and ε4 alleles. These results suggest that the effects ofAPOEon the ERC network are closely linked to the role of this gene on AD risk, which aMCI with ε4-carriers can accelerate the pathological progression of network-based mechanisms while ε2-carriers may play a protective role in contributing to a compensatory mechanism. It further suggests that APOE can appear to directly affect the ERC-MTG neural pathway associated with the impairment of episodic memory in aMCI.
Highlights
Mild cognitive impairment (MCI), as a high-risk factor for dementia due to Alzheimer’s disease (AD), is characterized by the disruption of episodic memory formation and is usually thought to reflect a transitional state between normal aging and dementia due to AD [1, 2], and can be further classified into subtypes including amnestic MCI/non-amnestic MCI and single/multidomain MCI [3, 4]
This study was to investigate the effects of APOEε2 and ε4 alleles on functional connectivity (FC) of entorhinal cortex (ERC) network and cognition in amnestic MCI (aMCI) and to delineate the intrinsic FC patterns of the ERC with large-scale cortical networks
AMCI showed the differentially altered FC patterns of the ERC network among the APOE2, APOE3, and APOE4 compared to healthy controls (HC)
Summary
Mild cognitive impairment (MCI), as a high-risk factor for dementia due to Alzheimer’s disease (AD), is characterized by the disruption of episodic memory formation and is usually thought to reflect a transitional state between normal aging and dementia due to AD [1, 2], and can be further classified into subtypes including amnestic MCI (aMCI)/non-amnestic MCI (naMCI) and single/multidomain MCI [3, 4]. The aMCI-multiple domain is consistently considered to have a higher conversion rate to AD compared to other MCI subtypes [5, 6]. It is well-known that the entorhinal cortex (ERC) is one of the earliest brain regions of AD pathology [7], in concert with the hippocampus, and plays a pivotal role in the normal formation of episodic memory [8]. It still remains unknown about the role of ERC network for revealing potential network-based disease mechanisms in aMCI
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
