TY - JOUR
T1 - Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer’s disease
AU - Alzheimer’s Disease Neuroimaging Initiative Consortium
AU - Williamson, Jordan N.
AU - James, Shirley A.
AU - Mullen, Sean P.
AU - Sutton, Bradley P.
AU - Wszalek, Tracey
AU - Mulyana, Beni
AU - Mukli, Peter
AU - Yabluchanskiy, Andriy
AU - Raj, Balebail Ashok
AU - Fargher, Kristin
AU - Smith, Amanda
AU - Raudin, Lisa
AU - Chaing, Gloria
AU - Relkin, Norman
AU - Smith, Karen Elizabeth
AU - Shim, Hyungsub
AU - Ponto, Laura L.Boles
AU - Schultz, Susan K.
AU - Sarrael, Antero
AU - Hernando, Raymundo
AU - Pomara, Nunzio
AU - Drost, Dick
AU - Kertesz, Andrew
AU - Rogers, John
AU - Rachinsky, Irina
AU - Pasternak, Stephen
AU - Finger, Elizabether
AU - Bachman, David
AU - Spicer, Kenneth
AU - Mintzer, Jacobo
AU - Miller, Bruce L.
AU - Rosen, Howard J.
AU - Correia, Stephen
AU - Malloy, Paul
AU - Salloway, Stephen
AU - Tremont, Geoffrey
AU - Querfurth, Henry
AU - Ott, Brian R.
AU - Watkins, Franklin
AU - Garg, Pradeep
AU - Williamson, Jeff D.
AU - Sink, Kaycee M.
AU - Schwartz, Eben S.
AU - Kitzmiller, Tamar J.
AU - Santulli, Robert B.
AU - Anderson, Karen
AU - Blank, Karen
AU - Pearlson, Godfrey D.
AU - Brown, Alice D.
AU - Shah, Raj C.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to American Aging Association 2024.
PY - 2024/12
Y1 - 2024/12
N2 - As of 2023, it is estimated that 6.7 million individuals in the United States live with Alzheimer’s disease (AD). Prior research indicates that AD disproportionality affects females; females have a greater incidence rate, perform worse on a variety of neuropsychological tasks, and have greater total brain atrophy. Recent research shows that hippocampal functional connectivity differs by sex and may be related to the observed sex differences in AD, and apolipoprotein E (ApoE) ε4 carriers have reduced hippocampal functional connectivity. The purpose of this study was to determine if the ApoE genotype plays a role in the observed sex differences in hippocampal functional connectivity in Alzheimer’s disease. The resting state fMRI and T2 MRI of individuals with AD (n = 30, female = 15) and cognitively normal individuals (n = 30, female = 15) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using the functional connectivity toolbox (CONN). Our results demonstrated intrahippocampal functional connectivity differed between those without an ε4 allele and those with at least one ε4 allele in each group. Additionally, intrahippocampal functional connectivity differed only by sex when Alzheimer’s participants had at least one ε4 allele. These results improve our current understanding of the role of the interacting relationship between sex, ApoE genotype, and hippocampal function in AD. Understanding these biomarkers may aid in the development of sex-specific interventions for improved AD treatment.
AB - As of 2023, it is estimated that 6.7 million individuals in the United States live with Alzheimer’s disease (AD). Prior research indicates that AD disproportionality affects females; females have a greater incidence rate, perform worse on a variety of neuropsychological tasks, and have greater total brain atrophy. Recent research shows that hippocampal functional connectivity differs by sex and may be related to the observed sex differences in AD, and apolipoprotein E (ApoE) ε4 carriers have reduced hippocampal functional connectivity. The purpose of this study was to determine if the ApoE genotype plays a role in the observed sex differences in hippocampal functional connectivity in Alzheimer’s disease. The resting state fMRI and T2 MRI of individuals with AD (n = 30, female = 15) and cognitively normal individuals (n = 30, female = 15) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using the functional connectivity toolbox (CONN). Our results demonstrated intrahippocampal functional connectivity differed between those without an ε4 allele and those with at least one ε4 allele in each group. Additionally, intrahippocampal functional connectivity differed only by sex when Alzheimer’s participants had at least one ε4 allele. These results improve our current understanding of the role of the interacting relationship between sex, ApoE genotype, and hippocampal function in AD. Understanding these biomarkers may aid in the development of sex-specific interventions for improved AD treatment.
KW - Alzheimer’s disease (AD)
KW - Apolipoprotein E
KW - Functional connectivity
KW - Sex difference
UR - http://www.scopus.com/inward/record.url?scp=85189982640&partnerID=8YFLogxK
U2 - 10.1007/s11357-024-01151-x
DO - 10.1007/s11357-024-01151-x
M3 - Article
C2 - 38598069
AN - SCOPUS:85189982640
SN - 2509-2715
VL - 46
SP - 6071
EP - 6084
JO - GeroScience
JF - GeroScience
IS - 6
ER -