Obstructive sleep apnea decreases central nervous system-derived proteins in the cerebrospinal fluid

Abstract

We hypothesized that one mechanism underlying the association between obstructive sleep apnea (OSA) and Alzheimer's disease is OSA leading to decreased slow wave activity (SWA), increased synaptic activity, decreased glymphatic clearance, and increased amyloid-β. Polysomnography and lumbar puncture were performed in OSA and control groups. SWA negatively correlated with cerebrospinal fluid (CSF) amyloid-β-40 among controls and was decreased in the OSA group. Unexpectedly, amyloid-β-40 was decreased in the OSA group. Other neuronally derived proteins, but not total protein, were also decreased in the OSA group, suggesting that OSA may affect the interaction between interstitial and cerebrospinal fluid. Ann Neurol 2016;80:154-159.

Figure 1. Slow wave activity and cerebrospinal fluid Amyloid-β-40

Slow wave activity, as measured by average delta power during non-rapid eye movement sleep, is negatively correlated with Aβ40 levels in the cerebrospinal fluid the following morning, in the Control group (n=29, Spearman’s r=−0.368, p=0.049). Values from the OSA group (n=10) do not have a significant correlation (Spearman’s r=0.152, p=0.676) and do not follow the same trend as the Control group. Aβ40 = amyloid-β-40. OSA = Obstructive sleep apnea.

Figure 2. Cerebrospinal fluid Amyloid-β and protein levels

CSF protein levels are plotted for each individual by group. Mean, standard deviation, and p values are listed in Table 1. Line indicates mean and bars denote standard error. Asterisks indicate p < 0.05. (A) Aβ40 and (B) Aβ42 are significantly lower in OSA compared to Control group. (C) Aβ42:Aβ40, an decrease of which is a sensitive marker of amyloid deposition, was not different between groups. There were strong trends for both (D) Tau and (E) pTau181 being lower in the OSA group. Neuronally-derived proteins (F) VILIP-1 and (G) neurogranin were significantly decreased in the OSA group, and (H) SNAP-25 trended lower also. Total protein (I) was not different between groups. OSA = Obstructive sleep apnea. Aβ40 = amyloid-β-40. Aβ42=amyloid-β-42. pTau181=phosphorylated Tau-181. VILIP-1 = Visinin-like protein 1. SNAP-25 = Synaptosomal-associated protein 25 kDa.