Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals

Neurobiol Aging. 2014 Jun;35(6):1318-24. doi: 10.1016/j.neurobiolaging.2013.12.030. Epub 2013 Dec 27.

Abstract

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

Keywords: Alzheimer's disease; Amyloid beta 42; ApoE; Biomarkers; CSF; Cerebral amyloid angiopathy; Elderly; Sleep-disordered breathing; p-tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoprotein E4 / genetics*
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / prevention & control
  • Continuous Positive Airway Pressure
  • Dementia / prevention & control
  • Female
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Respiration*
  • Sleep Wake Disorders / complications*
  • Sleep Wake Disorders / physiopathology*
  • Sleep Wake Disorders / therapy
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins