Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals.
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.
Center for Brain Health, NYU School of Medicine, New York, NY, USA; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain. Electronic address: Ricardo.Osorio@nyumc.org.
Ricardo S
RS
Osorio
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Indu
I
Ayappa
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Janna
J
Mantua
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Tyler
T
Gumb
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Andrew
A
Varga
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Anne M
AM
Mooney
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Omar E
OE
Burschtin
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Zachary
Z
Taxin
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Emmanuel
E
During
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Nicole
N
Spector
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Milton
M
Biagioni
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Elizabeth
E
Pirraglia
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Hiuyan
H
Lau
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik
H
Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj
K
Blennow
Department of Biostatistics, Rutgers School of Public Health, Piscataway, NJ, USA.
Shou-En
SE
Lu
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Lisa
L
Mosconi
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Lidia
L
Glodzik
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
David M
DM
Rapoport
Center for Brain Health, NYU School of Medicine, New York, NY, USA.
Mony J
MJ
de Leon
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000517:prevention & control; D045422:Continuous Positive Airway Pressure; D003704:Dementia / Q000517:prevention & control; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012119:Respiration; D012893:Sleep Wake Disorders / Q000150:complications* / Q000503:physiopathology* / Q000628:therapy; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer's disease; Amyloid beta 42; ApoE; Biomarkers; CSF; Cerebral amyloid angiopathy; Elderly; Sleep-disordered breathing; p-tau