PMID- 37511008
OWN - NLM
STAT- MEDLINE
DCOM- 20230807
LR  - 20230807
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 14
DP  - 2023 Jul 8
TI  - Cognitive Normal Older Adults with APOE-2 Allele Show a Distinctive Functional 
      Connectivity Pattern in Response to Cerebral Abeta Deposition.
LID - 10.3390/ijms241411250 [doi]
LID - 11250
AB  - The epsilon2 allele of apolipoprotein E (epsilon2) has neuroprotective effects against 
      beta-amyloid (Abeta) pathology in Alzheimer's disease (AD). However, its impact on 
      the functional connectivity and hub efficiency in cognitively normal older adults 
      (CN) with epsilon2 is unclear. We investigated the functional connectivity differences 
      in the default mode network (DMN), salience network, and central executive 
      network (CEN) between A-PET-negative (N = 29) and A-PET-positive (N = 15) CNs 
      with epsilon2/epsilon2 or epsilon2/epsilon3 genotypes. The A-PET-positive CNs exhibited a lower anterior 
      DMN functional connectivity, higher posterior DMN functional connectivity, and 
      increased CEN functional connectivity compared to the A-PET-negative CNs. 
      Cerebral Abeta retention was negatively correlated with anterior DMN functional 
      connectivity and positively correlated with posterior DMN and anterior CEN 
      functional connectivity. A graph theory analysis showed that the A-PET-positive 
      CNs displayed a higher betweenness centrality in the middle frontal gyrus (left) 
      and medial fronto-parietal regions (left). The betweenness centrality in the 
      middle frontal gyrus (left) was positively correlated with Abeta retention. Our 
      findings reveal a reversed anterior-posterior dissociation in the DMN functional 
      connectivity and heightened CEN functional connectivity in A-PET-positive CNs 
      with epsilon2. Hub efficiencies, measured by betweenness centrality, were increased in 
      the DMN and CEN of the A-PET-positive CNs with epsilon2. These results suggest unique 
      functional connectivity responses to Abeta pathology in CN individuals with epsilon2.
FAU - Wang, Sheng-Min
AU  - Wang SM
AD  - Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
FAU - Kang, Dong Woo
AU  - Kang DW
AUID- ORCID: 0000-0003-3289-075X
AD  - Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
FAU - Um, Yoo Hyun
AU  - Um YH
AD  - Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
FAU - Kim, Sunghwan
AU  - Kim S
AD  - Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
FAU - Kim, Regina E Y
AU  - Kim REY
AUID- ORCID: 0000-0003-2578-0069
AD  - Research Institute, Neurophet Inc., Seoul 08380, Republic of Korea.
FAU - Kim, Donghyeon
AU  - Kim D
AD  - Research Institute, Neurophet Inc., Seoul 08380, Republic of Korea.
FAU - Lee, Chang Uk
AU  - Lee CU
AUID- ORCID: 0000-0001-6398-7330
AD  - Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
FAU - Lim, Hyun Kook
AU  - Lim HK
AUID- ORCID: 0000-0001-8742-3409
AD  - Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The 
      Catholic University of Korea, Seoul 06591, Republic of Korea.
LA  - eng
GR  - No. 2022R1A2C1093215/National Research Foundation of Korea/
GR  - HU20C0315/Korea Health Industry Development Institute/Republic of Korea
PT  - Journal Article
DEP - 20230708
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Apolipoprotein E2)
RN  - 0 (Amyloid beta-Peptides)
SB  - IM
MH  - Aged
MH  - Humans
MH  - Alleles
MH  - *Alzheimer Disease/genetics
MH  - *Apolipoprotein E2/genetics
MH  - Brain/pathology
MH  - Cognition
MH  - Magnetic Resonance Imaging/methods
MH  - *Amyloid beta-Peptides/metabolism
PMC - PMC10380008
OTO - NOTNLM
OT  - APOE
OT  - Alzheimer's disease
OT  - beta-amyloid
OT  - central executive network
OT  - default mode network
OT  - functional MRI
OT  - graph theory
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:46
MHDA- 2023/07/31 11:42
PMCR- 2023/07/08
CRDT- 2023/07/29 01:21
PHST- 2023/05/30 00:00 [received]
PHST- 2023/06/29 00:00 [revised]
PHST- 2023/07/07 00:00 [accepted]
PHST- 2023/07/31 11:42 [medline]
PHST- 2023/07/29 11:46 [pubmed]
PHST- 2023/07/29 01:21 [entrez]
PHST- 2023/07/08 00:00 [pmc-release]
AID - ijms241411250 [pii]
AID - ijms-24-11250 [pii]
AID - 10.3390/ijms241411250 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jul 8;24(14):11250. doi: 10.3390/ijms241411250.