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Cereb Cortex. 2019 Nov 11. pii: bhz228. doi: 10.1093/cercor/bhz228. [Epub ahead of print]

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

Author information

1
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo 0317, Norway.
2
Department of Radiology and Nuclear Medicine, Oslo University Hospital, OSLO 0424, Norway.
3
Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Norway.
4
Lübeck Interdiscliplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck 23562, Germany.
5
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 43 180, Sweden.
6
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal 43 141, Sweden.
7
Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK.
8
UK Dementia Research Institute at UCL, London, London WC1E 6BT, UK.

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.

KEYWORDS:

HOMER1 ; Alzheimer’s disease; amyloid; gene expression; sleep

PMID:
32142100
DOI:
10.1093/cercor/bhz228

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