Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer’s disease

doi:10.1038/s41467-025-60748-8

Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer’s disease

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Abstract

Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer’s disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.

Original language	English
Article number	5905
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-60748-8
State	Published - Dec 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

We gratefully thank all the ADNI participants and staff for their contributions to data acquisition. This work was supported by the National Science Foundation of China (No. 82122023, U22A20294 to X.-L. Bu), the Science and Technology Innovation 2030 Major Projects (No. 2022ZD0211604-1 to X.-L. Bu), the Natural Science Foundation of Chongqing Municipality (No. CSTB2023NSCQ-JQX0019 to X.-L. Bu), and the Project of Sichuan Department of Science and Technology (No. 2023YFS0267 to Y. Xiang, 2022NSFSC1374 to J.-L. Zhao). The investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. The Fig. 1 was created with Figdraw.com. We gratefully thank all the ADNI participants and staff for their contributions to data acquisition. This work was supported by the National Science Foundation of China (No. 82122023, U22A20294 to X.-L. Bu), the Science and Technology Innovation 2030 Major Projects (No. 2022ZD0211604-1 to X.-L. Bu), the Natural Science Foundation of Chongqing Municipality (No. CSTB2023NSCQ-JQX0019 to X.-L. Bu), and the Project of Sichuan Department of Science and Technology (No. 2023YFS0267 to Y. Xiang, 2022NSFSC1374 to J.-L. Zhao). The investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf . The Fig. was created with Figdraw.com.

Funders	Funder number
DoD Alzheimer's Disease Neuroimaging Initiative
Department of Science and Technology of Sichuan Province	2022NSFSC1374, 2023YFS0267
National Natural Science Foundation of China (NSFC)	2022ZD0211604-1, 82122023, U22A20294
Natural Science Foundation of Chongqing Municipality	CSTB2023NSCQ-JQX0019

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-025-60748-8

Cite this

@article{57b748181a2b418093aca01a7203d292,

title = "Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer{\textquoteright}s disease",

abstract = "Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer{\textquoteright}s disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.",

author = "Bu, \{Xian Le\} and Wei Zhu and Wang, \{Qing Hua\} and Liu, \{Zhuo Ting\} and Bao, \{Yun Yu\} and Bai, \{Yu Di\} and Li, \{Jiang Hui\} and Liu, \{Zhi Hao\} and Zhao, \{Jia Ling\} and Yang Xiang and Jin, \{Wang Sheng\} and Jun Wang and Xia Lei and Wang, \{Yan Jiang\} and Kristin Fargher and Raj, \{Balebali Ashok\} and Amanda Smith and Lisa Ravdin and Michael Lin and Gloria Chiang and Norman Relkin and Antero Sarrael and Raymundo Hernando and Nunzio Pomara and David Bachman and Kenneth Spicer and Jacobo Mintzer and David Perry and Miller, \{Bruce L.\} and Rosen, \{Howard J.\} and Stephen Correia and Paul Malloy and Stephen Salloway and Geoffrey Tremont and Henry Querfurt and Ott, \{Brian R.\} and Franklin Watkins and Pradeep Garg and Williamson, \{Jeff D.\} and Leslie Gordineer and Sink, \{Kaycee M.\} and Santulli, \{Robert B.\} and Hynes, \{Mary L.\} and Marc Seltzer and Flashman, \{Laura A.\} and Karen Anderson and Karen Blank and Pearlson, \{Godfrey D.\} and Brown, \{Alice D.\} and Greg Jicha",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

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AU - Zhu, Wei

AU - Wang, Qing Hua

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AU - Bao, Yun Yu

AU - Bai, Yu Di

AU - Li, Jiang Hui

AU - Liu, Zhi Hao

AU - Zhao, Jia Ling

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AU - Jin, Wang Sheng

AU - Wang, Jun

AU - Lei, Xia

AU - Wang, Yan Jiang

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AU - Raj, Balebali Ashok

AU - Smith, Amanda

AU - Ravdin, Lisa

AU - Lin, Michael

AU - Chiang, Gloria

AU - Relkin, Norman

AU - Sarrael, Antero

AU - Hernando, Raymundo

AU - Pomara, Nunzio

AU - Bachman, David

AU - Spicer, Kenneth

AU - Mintzer, Jacobo

AU - Perry, David

AU - Miller, Bruce L.

AU - Rosen, Howard J.

AU - Correia, Stephen

AU - Malloy, Paul

AU - Salloway, Stephen

AU - Tremont, Geoffrey

AU - Querfurt, Henry

AU - Ott, Brian R.

AU - Watkins, Franklin

AU - Garg, Pradeep

AU - Williamson, Jeff D.

AU - Gordineer, Leslie

AU - Sink, Kaycee M.

AU - Santulli, Robert B.

AU - Hynes, Mary L.

AU - Seltzer, Marc

AU - Flashman, Laura A.

AU - Anderson, Karen

AU - Blank, Karen

AU - Pearlson, Godfrey D.

AU - Brown, Alice D.

AU - Jicha, Greg

PY - 2025/12

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N2 - Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer’s disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.

AB - Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer’s disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.

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DO - 10.1038/s41467-025-60748-8

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VL - 16

JO - Nature Communications

JF - Nature Communications

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ER -

Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer’s disease

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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