Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to beta-amyloid positivity

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Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to beta-amyloid positivity

Mander, B. A. (author)

Dave, A. (author)

Lui, K. K. (author)

Sprecher, K. E. (author)

Berisha, D. (author)

Chappel-Farley, M. G. (author)

Chen, I. Y. (author)

Riedner, B. A. (author)

Heston, M. (author)

Suridjan, I. (author)

Kollmorgen, G. (author)

Zetterberg, Henrik, 1973 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Blennow, Kaj, 1958 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Carlsson, C. M. (author)

Okonkwo, O. C. (author)

Asthana, S. (author)

Johnson, S. C. (author)

Bendlin, B. B. (author)

Benca, R. M. (author)

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(creator_code:org_t)

2022-06-07
2022
English.
In: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 45:9

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Study Objectives Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD. Methods Fifty-eight cognitively unimpaired, beta-amyloid-negative, older adults (mean +/- SD; 61.4 +/- 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) epsilon 4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, beta-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to <16Hz) sleep spindle measures through these AD biomarkers. Results Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE epsilon 4 genotype, apnea-hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates. Conclusions These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to beta-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Alzheimer's disease
sleep spindles
tau phosphorylation
inflammation
neurodegeneration
memory
free cluster-enhancement
age-related-changes
high-density eeg
nrem
slow waves
alzheimers-disease
dependent memory
diagnostic guidelines
current stimulation
national institute
spherical splines
Neurosciences & Neurology

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ref (subject category)
art (subject category)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

Articles in the publication: Sleep

By the university: University of Gothenburg

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