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

Journal article
Authors A. M. Fjell
D. Sederevicius
M. H. Sneve
A. M. G. De Lange
A. C. Brathen
A. V. Idland
L. O. Watne
Y. P. Wang
C. Reinbold
V. Dobricic
F. Kilpert
Kaj Blennow
Henrik Zetterberg
S. J. Hong
L. Bertram
K. B. Walhovd
Initia Alzheimers Dis Neuroimaging
Published in Cerebral Cortex
Volume 30
Issue 4
Pages 2144-2156
ISSN 1047-3211
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 2144-2156
Language en
Links dx.doi.org/10.1093/cercor/bhz228
Keywords Alzheimer's disease, amyloid, gene expression, HOMER1, sleep, surface-based analysis, alzheimers-disease, cerebral-cortex, hypothetical model, quality, beta, thickness, protein, body, neuroinflammation, Neurosciences & Neurology
Subject categories Neurosciences

Abstract

Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker beta-amyloid (AD) 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 Homerla, a neural protein coded by the HOMER1 gene, which has also been implicated in brain A beta accumulation. Here, we tested whether the relationship between cortical A beta 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, A beta 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-A beta relationship followed closely the A beta accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and A beta accumulation may involve Homer1 activity in the cortical regions, where harbor A beta deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

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