Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression

Anders M. Fjell; Donatas Sederevicius; Markus H. Sneve; Ann Marie Glasø De Lange; Anne Ceciliesjøli Bråthen; Ane Victoria Idland; Leiv Otto Watne; Yunpeng Wang; Céline Reinbold; Valerija Dobricic; Fabian Kilpert; Kaj Blennow; Henrik Zetterbergj; Shengjun Hong; Lars Bertram; Kristine B. Walhovd

doi:10.1093/cercor/bhz228

Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression

Anders M. Fjell^*, Donatas Sederevicius, Markus H. Sneve, Ann Marie Glasø De Lange, Anne Ceciliesjøli Bråthen, Ane Victoria Idland, Leiv Otto Watne, Yunpeng Wang, Céline Reinbold, Valerija Dobricic, Fabian Kilpert, Kaj Blennow, Henrik Zetterbergj, Shengjun Hong, Lars Bertram, Kristine B. Walhovd

^*Corresponding author for this work

Institute of Neurogenetics

15 Citations (Scopus)

Abstract

Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker β-Amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

Original language	English
Journal	Cerebral Cortex
Volume	30
Issue number	4
Pages (from-to)	2144-2156
Number of pages	13
ISSN	1047-3211
DOIs	https://doi.org/10.1093/cercor/bhz228
Publication status	Published - 14.04.2020

Funding

The National Association for Public Health’s dementia research program, the Department of Psychology at the University of Oslo, the Norwegian Research Council, the Medical Student Research Program at the University of Oslo, and the project has received funding from the European Research Council’s Starting Grant and Consolidator Grant scheme under grant agreements 283634, 725025, and 313440. Additional funding for parts of the study was received from Innlandet Hospital Trust (grant number: 150201), the Knut and Alice Wallenberg Foundation, the European Research Council (#681712), the Swedish Research Council (grant numbers: #2018-02532, 2017-0095 and K2013-61X-14002-13-5), the TorstenSöderberg Foundation (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (grant #ALFGBG-715986# and #ALFGBG-720931). The MCI/AD PET data collection and sharing was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12- The authors would also like to thank the study participants, and acknowledge the contributions of the Department of Gynecology, the Department of Urology, the Department of Orthopedic Surgery, the Department of Geriatric Medicine and the Department of Anesthesiology at Oslo University Hospital, and the Department of Orthopedic Surgery and the Department of Anesthesiology at Diakonhjemmet Hospital in Oslo, Norway. We thank MrsTanjaWesse and SanazSedghpourSabet as well as Drs Michael Wittig and Andre Franke at the Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany for technical assistance with the GSA genotyping. The LIGA team acknowledges computational support from the OMICS compute cluster at the University of Lübeck. Conflicts of Interest: None declared.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Medical Genetics

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10.1093/cercor/bhz228

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Fjell, A. M., Sederevicius, D., Sneve, M. H., De Lange, A. M. G., Bråthen, A. C., Idland, A. V., Watne, L. O., Wang, Y., Reinbold, C., Dobricic, V., Kilpert, F., Blennow, K., Zetterbergj, H., Hong, S., Bertram, L., & Walhovd, K. B. (2020). Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression. Cerebral Cortex, 30(4), 2144-2156. https://doi.org/10.1093/cercor/bhz228

@article{92a2eab36b16415a964debc129190a23,

title = "Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression",

abstract = "Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker β-Amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.",

author = "Fjell, \{Anders M.\} and Donatas Sederevicius and Sneve, \{Markus H.\} and \{De Lange\}, \{Ann Marie Glas{\o}\} and Br{\aa}then, \{Anne Ceciliesj{\o}li\} and Idland, \{Ane Victoria\} and Watne, \{Leiv Otto\} and Yunpeng Wang and C{\'e}line Reinbold and Valerija Dobricic and Fabian Kilpert and Kaj Blennow and Henrik Zetterbergj and Shengjun Hong and Lars Bertram and Walhovd, \{Kristine B.\}",

note = "Funding Information: The National Association for Public Health{\textquoteright}s dementia research program, the Department of Psychology at the University of Oslo, the Norwegian Research Council, the Medical Student Research Program at the University of Oslo, and the project has received funding from the European Research Council{\textquoteright}s Starting Grant and Consolidator Grant scheme under grant agreements 283634, 725025, and 313440. Additional funding for parts of the study was received from Innlandet Hospital Trust (grant number: 150201), the Knut and Alice Wallenberg Foundation, the European Research Council (\#681712), the Swedish Research Council (grant numbers: \#2018-02532, 2017-0095 and K2013-61X-14002-13-5), the TorstenS{\"o}derberg Foundation (\#2017-00915), the Swedish Alzheimer Foundation (\#AF-742881), Hj{\"a}rnfonden, Sweden (\#FO2017-0243), and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (grant \#ALFGBG-715986\# and \#ALFGBG-720931). The MCI/AD PET data collection and sharing was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12- Funding Information: The authors would also like to thank the study participants, and acknowledge the contributions of the Department of Gynecology, the Department of Urology, the Department of Orthopedic Surgery, the Department of Geriatric Medicine and the Department of Anesthesiology at Oslo University Hospital, and the Department of Orthopedic Surgery and the Department of Anesthesiology at Diakonhjemmet Hospital in Oslo, Norway. We thank MrsTanjaWesse and SanazSedghpourSabet as well as Drs Michael Wittig and Andre Franke at the Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany for technical assistance with the GSA genotyping. The LIGA team acknowledges computational support from the OMICS compute cluster at the University of L{\"u}beck. Conflicts of Interest: None declared. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = apr,

day = "14",

doi = "10.1093/cercor/bhz228",

language = "English",

volume = "30",

pages = "2144--2156",

journal = "Cerebral Cortex",

issn = "1047-3211",

publisher = "Oxford University Press",

number = "4",

}

Fjell, AM, Sederevicius, D, Sneve, MH, De Lange, AMG, Bråthen, AC, Idland, AV, Watne, LO, Wang, Y, Reinbold, C, Dobricic, V, Kilpert, F, Blennow, K, Zetterbergj, H, Hong, S, Bertram, L & Walhovd, KB 2020, 'Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression', Cerebral Cortex, vol. 30, no. 4, pp. 2144-2156. https://doi.org/10.1093/cercor/bhz228

TY - JOUR

T1 - Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression

AU - Fjell, Anders M.

AU - Sederevicius, Donatas

AU - Sneve, Markus H.

AU - De Lange, Ann Marie Glasø

AU - Bråthen, Anne Ceciliesjøli

AU - Idland, Ane Victoria

AU - Watne, Leiv Otto

AU - Wang, Yunpeng

AU - Reinbold, Céline

AU - Dobricic, Valerija

AU - Kilpert, Fabian

AU - Blennow, Kaj

AU - Zetterbergj, Henrik

AU - Hong, Shengjun

AU - Bertram, Lars

AU - Walhovd, Kristine B.

N1 - Funding Information: The National Association for Public Health’s dementia research program, the Department of Psychology at the University of Oslo, the Norwegian Research Council, the Medical Student Research Program at the University of Oslo, and the project has received funding from the European Research Council’s Starting Grant and Consolidator Grant scheme under grant agreements 283634, 725025, and 313440. Additional funding for parts of the study was received from Innlandet Hospital Trust (grant number: 150201), the Knut and Alice Wallenberg Foundation, the European Research Council (#681712), the Swedish Research Council (grant numbers: #2018-02532, 2017-0095 and K2013-61X-14002-13-5), the TorstenSöderberg Foundation (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (grant #ALFGBG-715986# and #ALFGBG-720931). The MCI/AD PET data collection and sharing was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12- Funding Information: The authors would also like to thank the study participants, and acknowledge the contributions of the Department of Gynecology, the Department of Urology, the Department of Orthopedic Surgery, the Department of Geriatric Medicine and the Department of Anesthesiology at Oslo University Hospital, and the Department of Orthopedic Surgery and the Department of Anesthesiology at Diakonhjemmet Hospital in Oslo, Norway. We thank MrsTanjaWesse and SanazSedghpourSabet as well as Drs Michael Wittig and Andre Franke at the Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany for technical assistance with the GSA genotyping. The LIGA team acknowledges computational support from the OMICS compute cluster at the University of Lübeck. Conflicts of Interest: None declared. Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/4/14

Y1 - 2020/4/14

N2 - Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker β-Amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

AB - Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker β-Amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

UR - https://www.scopus.com/pages/publications/85083913938

U2 - 10.1093/cercor/bhz228

DO - 10.1093/cercor/bhz228

M3 - Journal articles

C2 - 32142100

AN - SCOPUS:85083913938

SN - 1047-3211

VL - 30

SP - 2144

EP - 2156

JO - Cerebral Cortex

JF - Cerebral Cortex

IS - 4

ER -

Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression

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