Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity
| Autor: | Bryce A Mander, Abhishek Dave, Kitty K Lui, Katherine E Sprecher, Destiny Berisha, Miranda G Chappel-Farley, Ivy Y Chen, Brady A Riedner, Margo Heston, Ivonne Suridjan, Gwendlyn Kollmorgen, Henrik Zetterberg, Kaj Blennow, Cynthia M Carlsson, Ozioma C Okonkwo, Sanjay Asthana, Sterling C Johnson, Barbara B Bendlin, Ruth M Benca |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Aging Apolipoprotein E4 tau Proteins Neurodegenerative Alzheimer's Disease Medical and Health Sciences memory Alzheimer Disease Physiology (medical) Acquired Cognitive Impairment Genetics Humans 2.1 Biological and endogenous factors Cognitive Dysfunction Aetiology Aged Inflammation Amyloid beta-Peptides Neurology & Neurosurgery tau phosphorylation Psychology and Cognitive Sciences neurodegeneration Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Middle Aged Biological Sciences Peptide Fragments sleep spindles Brain Disorders Neurological Sleep Across the Lifespan Female Dementia Neurology (clinical) Sleep Sleep Research Alzheimer’s disease Biomarkers |
| Zdroj: | Sleep Sleep, vol 45, iss 9 |
| ISSN: | 1550-9109 0161-8105 |
| DOI: | 10.1093/sleep/zsac135 |
| Popis: | 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, β-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) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, β-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 Results Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE ε4 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 β-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD. |
| Databáze: | OpenAIRE |
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