Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease

Sára Nemes; Paige E. Logan; Mohit K. Manchella; Nidhi S. Mundada; Renaud La Joie; Angelina J. Polsinelli; Dustin B. Hammers; Robert A. Koeppe; Tatiana M. Foroud; Kelly N. Nudelman; Ani Eloyan; Leonardo Iaccarino; Valérie Dorsant-Ardón; Alexander Taurone; Maryanne Thangarajah; Jeffery L. Dage; Paul Aisen; Lea T. Grinberg; Clifford R. Jack; Joel Kramer; Walter A. Kukull; Melissa E. Murray; Malia Rumbaugh; David N. Soleimani-Meigooni; Arthur Toga; Alexandra Touroutoglou; Prashanthi Vemuri; Alireza Atri; Gregory S. Day; Ranjan Duara; Neill R. Graff-Radford; Lawrence S. Honig; David T. Jones; Joseph Masdeu; Mario F. Mendez; Erik Musiek; Chiadi U. Onyike; Meghan Riddle; Emily Rogalski; Stephen Salloway; Sharon J. Sha; Raymond S. Turner; Thomas S. Wingo; Kyle B. Womack; David A. Wolk; Gil D. Rabinovici; Maria C. Carrillo; Bradford C. Dickerson; Liana G. Apostolova

doi:10.1002/alz.13403

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease

Sára Nemes, Paige E. Logan, Mohit K. Manchella, Nidhi S. Mundada, Renaud La Joie, Angelina J. Polsinelli, Dustin B. Hammers, Robert A. Koeppe, Tatiana M. Foroud, Kelly N. Nudelman, Ani Eloyan, Leonardo Iaccarino, Valérie Dorsant-Ardón, Alexander Taurone, Maryanne Thangarajah, Jeffery L. Dage, Paul Aisen, Lea T. Grinberg, Clifford R. Jack, Joel KramerWalter A. Kukull, Melissa E. Murray, Malia Rumbaugh, David N. Soleimani-Meigooni, Arthur Toga, Alexandra Touroutoglou, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Lawrence S. Honig, David T. Jones, Joseph Masdeu, Mario F. Mendez, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon J. Sha, Raymond S. Turner, Thomas S. Wingo, Kyle B. Womack, David A. Wolk, Gil D. Rabinovici, Maria C. Carrillo, Bradford C. Dickerson, Liana G. Apostolova

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

2 Scopus citations

Abstract

INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

Original language	English (US)
Pages (from-to)	S49-S63
Journal	Alzheimer's and Dementia
Volume	19
Issue number	S9
DOIs	https://doi.org/10.1002/alz.13403
State	Published - Nov 2023

Keywords

APOE ε4
MRI
amyloid PET
early-onset Alzheimer's disease
early-onset non-Alzheimer's disease
genetics
imaging biomarkers
neuroimaging
sex differences
tau PET

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.13403

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Nemes, S., Logan, P. E., Manchella, M. K., Mundada, N. S., La Joie, R., Polsinelli, A. J., Hammers, D. B., Koeppe, R. A., Foroud, T. M., Nudelman, K. N., Eloyan, A., Iaccarino, L., Dorsant-Ardón, V., Taurone, A., Thangarajah, M., Dage, J. L., Aisen, P., Grinberg, L. T., Jack, C. R., ... Apostolova, L. G. (2023). Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease. Alzheimer's and Dementia, 19(S9), S49-S63. https://doi.org/10.1002/alz.13403

Nemes, S, Logan, PE, Manchella, MK, Mundada, NS, La Joie, R, Polsinelli, AJ, Hammers, DB, Koeppe, RA, Foroud, TM, Nudelman, KN, Eloyan, A, Iaccarino, L, Dorsant-Ardón, V, Taurone, A, Thangarajah, M, Dage, JL, Aisen, P, Grinberg, LT, Jack, CR, Kramer, J, Kukull, WA, Murray, ME, Rumbaugh, M, Soleimani-Meigooni, DN, Toga, A, Touroutoglou, A, Vemuri, P, Atri, A, Day, GS, Duara, R, Graff-Radford, NR, Honig, LS, Jones, DT, Masdeu, J, Mendez, MF, Musiek, E, Onyike, CU, Riddle, M, Rogalski, E, Salloway, S, Sha, SJ, Turner, RS, Wingo, TS, Womack, KB, Wolk, DA, Rabinovici, GD, Carrillo, MC, Dickerson, BC & Apostolova, LG 2023, 'Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease', Alzheimer's and Dementia, vol. 19, no. S9, pp. S49-S63. https://doi.org/10.1002/alz.13403

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title = "Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease",

abstract = "INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.",

keywords = "APOE ε4, MRI, amyloid PET, early-onset Alzheimer's disease, early-onset non-Alzheimer's disease, genetics, imaging biomarkers, neuroimaging, sex differences, tau PET",

author = "S{\'a}ra Nemes and Logan, {Paige E.} and Manchella, {Mohit K.} and Mundada, {Nidhi S.} and {La Joie}, Renaud and Polsinelli, {Angelina J.} and Hammers, {Dustin B.} and Koeppe, {Robert A.} and Foroud, {Tatiana M.} and Nudelman, {Kelly N.} and Ani Eloyan and Leonardo Iaccarino and Val{\'e}rie Dorsant-Ard{\'o}n and Alexander Taurone and Maryanne Thangarajah and Dage, {Jeffery L.} and Paul Aisen and Grinberg, {Lea T.} and Jack, {Clifford R.} and Joel Kramer and Kukull, {Walter A.} and Murray, {Melissa E.} and Malia Rumbaugh and Soleimani-Meigooni, {David N.} and Arthur Toga and Alexandra Touroutoglou and Prashanthi Vemuri and Alireza Atri and Day, {Gregory S.} and Ranjan Duara and Graff-Radford, {Neill R.} and Honig, {Lawrence S.} and Jones, {David T.} and Joseph Masdeu and Mendez, {Mario F.} and Erik Musiek and Onyike, {Chiadi U.} and Meghan Riddle and Emily Rogalski and Stephen Salloway and Sha, {Sharon J.} and Turner, {Raymond S.} and Wingo, {Thomas S.} and Womack, {Kyle B.} and Wolk, {David A.} and Rabinovici, {Gil D.} and Carrillo, {Maria C.} and Dickerson, {Bradford C.} and Apostolova, {Liana G.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = nov,

doi = "10.1002/alz.13403",

language = "English (US)",

volume = "19",

pages = "S49--S63",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier",

number = "S9",

}

TY - JOUR

T1 - Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease

AU - Nemes, Sára

AU - Logan, Paige E.

AU - Manchella, Mohit K.

AU - Mundada, Nidhi S.

AU - La Joie, Renaud

AU - Polsinelli, Angelina J.

AU - Hammers, Dustin B.

AU - Koeppe, Robert A.

AU - Foroud, Tatiana M.

AU - Nudelman, Kelly N.

AU - Eloyan, Ani

AU - Iaccarino, Leonardo

AU - Dorsant-Ardón, Valérie

AU - Taurone, Alexander

AU - Thangarajah, Maryanne

AU - Dage, Jeffery L.

AU - Aisen, Paul

AU - Grinberg, Lea T.

AU - Jack, Clifford R.

AU - Kramer, Joel

AU - Kukull, Walter A.

AU - Murray, Melissa E.

AU - Rumbaugh, Malia

AU - Soleimani-Meigooni, David N.

AU - Toga, Arthur

AU - Touroutoglou, Alexandra

AU - Vemuri, Prashanthi

AU - Atri, Alireza

AU - Day, Gregory S.

AU - Duara, Ranjan

AU - Graff-Radford, Neill R.

AU - Honig, Lawrence S.

AU - Jones, David T.

AU - Masdeu, Joseph

AU - Mendez, Mario F.

AU - Musiek, Erik

AU - Onyike, Chiadi U.

AU - Riddle, Meghan

AU - Rogalski, Emily

AU - Salloway, Stephen

AU - Sha, Sharon J.

AU - Turner, Raymond S.

AU - Wingo, Thomas S.

AU - Womack, Kyle B.

AU - Wolk, David A.

AU - Rabinovici, Gil D.

AU - Carrillo, Maria C.

AU - Dickerson, Bradford C.

AU - Apostolova, Liana G.

PY - 2023/11

Y1 - 2023/11

N2 - INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

AB - INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

KW - APOE ε4

KW - MRI

KW - amyloid PET

KW - early-onset Alzheimer's disease

KW - early-onset non-Alzheimer's disease

KW - genetics

KW - imaging biomarkers

KW - neuroimaging

KW - sex differences

KW - tau PET

UR - http://www.scopus.com/inward/record.url?scp=85166009080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85166009080&partnerID=8YFLogxK

U2 - 10.1002/alz.13403

DO - 10.1002/alz.13403

M3 - Article

C2 - 37496307

AN - SCOPUS:85166009080

SN - 1552-5260

VL - 19

SP - S49-S63

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - S9

ER -

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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