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<jats:title>Abstract</jats:title><jats:p>Older adults who report more sleep problems tend to have elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ), but the mechanisms responsible for this relationship are largely unknown. Molecular markers of sleep problems are now emerging from rodent research, yielding opportunities to generate hypotheses about the causes of the sleep-Aβ relationship. A major molecular marker of sleep deprivation is Homer1a, a neural protein coded by the <jats:italic>HOMER1</jats:italic> gene, involved in control of sleep homeostasis and also implied in Aβ accumulation. Here, in a sample of 109 cognitively healthy middle-aged and older adults, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over three years, was stronger in cortical regions with high <jats:italic>HOMER1</jats:italic> mRNA expression levels. Aβ correlated with poorer sleep quality cross-sectionally and longitudinally. This relationship was stronger in the younger (50-67 years) than the older (68-81 years) participants. Effects were mainly found in regions with high expression of <jats:italic>HOMER1</jats:italic>, suggesting a possible molecular pathway between sleep problems and Aβ accumulation. The anatomical distribution of the sleep-Aβ relationships followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment (MCI) or AD. Thus, the results indicate that the relationship between sleep problems and Aβ-accumulation may involve Homer1 activity in the cortical regions that harbor Aβ in AD. Analysis of cortical gene expression patterns represent a promising avenue to unveil molecular mechanisms behind the relationship between sleep problems and AD risk.</jats:p>

Original publication

DOI

10.1101/335612

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

31/05/2018