Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer’s disease

Alzheimer’s Disease Neuroimaging Initiative Consortium

doi:10.1007/s11357-024-01151-x

Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer’s disease

Alzheimer’s Disease Neuroimaging Initiative Consortium

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	6071-6084
Number of pages	14
Journal	GeroScience
Volume	46
Issue number	6
DOIs	https://doi.org/10.1007/s11357-024-01151-x
State	Published - Dec 2024

Keywords

Alzheimer’s disease (AD)
Apolipoprotein E
Functional connectivity
Sex difference

Access to Document

10.1007/s11357-024-01151-x

Cite this

@article{a808f6e18085483eb8be0310ca6652f3,

title = "Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer{\textquoteright}s disease",

abstract = "As of 2023, it is estimated that 6.7 million individuals in the United States live with Alzheimer{\textquoteright}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{\textquoteright}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{\textquoteright}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{\textquoteright}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.",

keywords = "Alzheimer{\textquoteright}s disease (AD), Apolipoprotein E, Functional connectivity, Sex difference",

author = "{Alzheimer{\textquoteright}s Disease Neuroimaging Initiative Consortium} and Williamson, {Jordan N.} and James, {Shirley A.} and Mullen, {Sean P.} and Sutton, {Bradley P.} and Tracey Wszalek and Beni Mulyana and Peter Mukli and Andriy Yabluchanskiy and Raj, {Balebail Ashok} and Kristin Fargher and Amanda Smith and Lisa Raudin and Gloria Chaing and Norman Relkin and Smith, {Karen Elizabeth} and Hyungsub Shim and Ponto, {Laura L.Boles} and Schultz, {Susan K.} and Antero Sarrael and Raymundo Hernando and Nunzio Pomara and Dick Drost and Andrew Kertesz and John Rogers and Irina Rachinsky and Stephen Pasternak and Elizabether Finger and David Bachman and Kenneth Spicer and Jacobo Mintzer and Miller, {Bruce L.} and Rosen, {Howard J.} and Stephen Correia and Paul Malloy and Stephen Salloway and Geoffrey Tremont and Henry Querfurth and Ott, {Brian R.} and Franklin Watkins and Pradeep Garg and Williamson, {Jeff D.} and Sink, {Kaycee M.} and Schwartz, {Eben S.} and Kitzmiller, {Tamar J.} and Santulli, {Robert B.} and Karen Anderson and Karen Blank and Pearlson, {Godfrey D.} and Brown, {Alice D.} and Dzintra Celmins and Zimmerman, {Earl A.} and Anahita Adeli and Maria Kataki and Scharre, {Douglas W.} and Michelle Rainka and Horacio Capote and Vernice Bates and Stephanie Reeder and Adam Fleisher and Pierre Tariot and Dana Nguyen and Adrian Preda and Potkin, {Steven G.} and Carlsson, {Cynthia M.} and Sanjay Asthana and Sterling Johnson and Rob Bartha and Lee, {T. Y.} and Michael Borrie and Smita Kittur and Charles DeCarli and John Olichney and Owen Carmichael and Evan Fletcher and Leon Hudson and Paula Ogrocki and Alan Lerner and Joanne Allard and Saba Wolday and Obisesan, {Thomas O.} and Johnson, {Patricia Lynn} and Alexander Norbash and Budson, {Andrew E.} and Ronald Killiany and Neil Kowall and Sirrel, {Sherye A.} and Jacobson, {Sandra A.} and Belden, {Christine M.} and Sabbagh, {Marwan N.} and Jared Tinklenberg and Allyson Rosen and Barton Lane and Taylor, {Joy L.} and Jerome Yesavage and Meghan Frey and Gad Marshall and Johnson, {Keith A.} and Sperling, {Reisa A.} and Brigid Reynolds and Kathleen Johnson and Turner, {Raymond Scott} and Teresa Villena and Walter Martinez and Carl Sadowsky and Nancy Johnson and Wu, {Chuang Kuo} and Kristine Lipowski and Mesulam, {Marek Marsel} and Diana Kerwin and Donna Munic and Charles Bernick and Dick Trost and Past, {Michele Assaly} and Benita Mudge and Howard Feldman and Hsiung, {Ging Yuek Robin} and Curtis Caldwell and Bojana Stefanovic and Sandra Black and Chris Hosein and Howard Bergman and Howard Chertkow and MacAvoy, {Martha G.} and Carson, {Richard E.} and {van Dyck}, {Christopher H.} and Cynthia Hunt and Scott Herring and Matthews, {Brandy R.} and Hake, {Ann Marie} and Farlow, {Martin R.} and Heather Johnson and Tracy Kendall and Francine Parfitt and Radford, {Neill R.Graff} and George Bartzokis and Lu, {Po H.} and Silverman, {Daniel H.S.} and Ellen Woo and Kathleen Tingus and Liana Apostolova and Swerdlow, {Russell H.} and Anderson, {Heather S.} and Burns, {Jeffrey M.} and Cellar, {Janet S.} and Lah, {James J.} and Levey, {Allan I.} and Michael DeVous and Cook, {Kristen Martin} and Myron Weiner and Richard King and Arrastia, {Ramon Diaz} and Mary Quiceno and Dana Mathews and Kyle Womack and {Mc Adams Ortiz}, Catherine and Gaby Thai and Mulnard, {Ruth A.} and Connie Brand and Ismail, {M. Saleem} and Makino, {Kelly M.} and Kim Martin and Goldstein, {Bonnie S.} and Porsteinsson, {Anton P.} and Simpson, {Donna M.} and Oakley, {Mary Ann} and Lopez, {Oscar L.} and Gary Conrad and Elizabeth Oates and Partha Sinha and Peter Hardy and Greg Jicha and Smith, {Charles D.} and Wolk, {David A.} and Karlawish, {Jason H.} and Arnold, {Steven E.} and Wong, {Terence Z.} and Petrella, {Jeffrey R.} and Doraiswamy, {P. Murali} and {De Santi}, Susan and Lidia Glodzik and {de Leon}, {Mony J.} and Henry Rusinek and Michel, {Christina A.} and Brittany Cerbone and Pogorele, {Dana M.} and Galvin, {James E.} and Stephanie Kielb and Daniel D{\textquoteright}Agostino and Chiadi Onyike and Marilyn Albert and Peggy Roberts and Greig, {Maria T.} and Daniel Varon and Ranjan Duara and Shah, {Raj C.} and Leyla deToledo-Morrell and Effie Mitsis and Hillel Grossman and Erik Roberson and Beau Ances",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to American Aging Association 2024.",

year = "2024",

month = dec,

doi = "10.1007/s11357-024-01151-x",

language = "English",

volume = "46",

pages = "6071--6084",

journal = "GeroScience",

issn = "2509-2715",

number = "6",

}

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 - Celmins, Dzintra

AU - Zimmerman, Earl A.

AU - Adeli, Anahita

AU - Kataki, Maria

AU - Scharre, Douglas W.

AU - Rainka, Michelle

AU - Capote, Horacio

AU - Bates, Vernice

AU - Reeder, Stephanie

AU - Fleisher, Adam

AU - Tariot, Pierre

AU - Nguyen, Dana

AU - Preda, Adrian

AU - Potkin, Steven G.

AU - Carlsson, Cynthia M.

AU - Asthana, Sanjay

AU - Johnson, Sterling

AU - Bartha, Rob

AU - Lee, T. Y.

AU - Borrie, Michael

AU - Kittur, Smita

AU - DeCarli, Charles

AU - Olichney, John

AU - Carmichael, Owen

AU - Fletcher, Evan

AU - Hudson, Leon

AU - Ogrocki, Paula

AU - Lerner, Alan

AU - Allard, Joanne

AU - Wolday, Saba

AU - Obisesan, Thomas O.

AU - Johnson, Patricia Lynn

AU - Norbash, Alexander

AU - Budson, Andrew E.

AU - Killiany, Ronald

AU - Kowall, Neil

AU - Sirrel, Sherye A.

AU - Jacobson, Sandra A.

AU - Belden, Christine M.

AU - Sabbagh, Marwan N.

AU - Tinklenberg, Jared

AU - Rosen, Allyson

AU - Lane, Barton

AU - Taylor, Joy L.

AU - Yesavage, Jerome

AU - Frey, Meghan

AU - Marshall, Gad

AU - Johnson, Keith A.

AU - Sperling, Reisa A.

AU - Reynolds, Brigid

AU - Johnson, Kathleen

AU - Turner, Raymond Scott

AU - Villena, Teresa

AU - Martinez, Walter

AU - Sadowsky, Carl

AU - Johnson, Nancy

AU - Wu, Chuang Kuo

AU - Lipowski, Kristine

AU - Mesulam, Marek Marsel

AU - Kerwin, Diana

AU - Munic, Donna

AU - Bernick, Charles

AU - Trost, Dick

AU - Past, Michele Assaly

AU - Mudge, Benita

AU - Feldman, Howard

AU - Hsiung, Ging Yuek Robin

AU - Caldwell, Curtis

AU - Stefanovic, Bojana

AU - Black, Sandra

AU - Hosein, Chris

AU - Bergman, Howard

AU - Chertkow, Howard

AU - MacAvoy, Martha G.

AU - Carson, Richard E.

AU - van Dyck, Christopher H.

AU - Hunt, Cynthia

AU - Herring, Scott

AU - Matthews, Brandy R.

AU - Hake, Ann Marie

AU - Farlow, Martin R.

AU - Johnson, Heather

AU - Kendall, Tracy

AU - Parfitt, Francine

AU - Radford, Neill R.Graff

AU - Bartzokis, George

AU - Lu, Po H.

AU - Silverman, Daniel H.S.

AU - Woo, Ellen

AU - Tingus, Kathleen

AU - Apostolova, Liana

AU - Swerdlow, Russell H.

AU - Anderson, Heather S.

AU - Burns, Jeffrey M.

AU - Cellar, Janet S.

AU - Lah, James J.

AU - Levey, Allan I.

AU - DeVous, Michael

AU - Cook, Kristen Martin

AU - Weiner, Myron

AU - King, Richard

AU - Arrastia, Ramon Diaz

AU - Quiceno, Mary

AU - Mathews, Dana

AU - Womack, Kyle

AU - Mc Adams Ortiz, Catherine

AU - Thai, Gaby

AU - Mulnard, Ruth A.

AU - Brand, Connie

AU - Ismail, M. Saleem

AU - Makino, Kelly M.

AU - Martin, Kim

AU - Goldstein, Bonnie S.

AU - Porsteinsson, Anton P.

AU - Simpson, Donna M.

AU - Oakley, Mary Ann

AU - Lopez, Oscar L.

AU - Conrad, Gary

AU - Oates, Elizabeth

AU - Sinha, Partha

AU - Hardy, Peter

AU - Jicha, Greg

AU - Smith, Charles D.

AU - Wolk, David A.

AU - Karlawish, Jason H.

AU - Arnold, Steven E.

AU - Wong, Terence Z.

AU - Petrella, Jeffrey R.

AU - Doraiswamy, P. Murali

AU - De Santi, Susan

AU - Glodzik, Lidia

AU - de Leon, Mony J.

AU - Rusinek, Henry

AU - Michel, Christina A.

AU - Cerbone, Brittany

AU - Pogorele, Dana M.

AU - Galvin, James E.

AU - Kielb, Stephanie

AU - D’Agostino, Daniel

AU - Onyike, Chiadi

AU - Albert, Marilyn

AU - Roberts, Peggy

AU - Greig, Maria T.

AU - Varon, Daniel

AU - Duara, Ranjan

AU - Shah, Raj C.

AU - deToledo-Morrell, Leyla

AU - Mitsis, Effie

AU - Grossman, Hillel

AU - Roberson, Erik

AU - Ances, Beau

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 -

Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer’s disease

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this