Letter to the editor regarding “Biomarkers of Alzheimer’s disease in severe obstructive sleep apnea–hypopnea syndrome in the Chinese population”

Abstract

I read the article titled “Biomarkers of Alzheimer’s disease in severe obstructive sleep apnea–hypopnea syndrome in the Chinese population” by Kong et al. with great interest [1]. The authors explored the level of Alzheimer’s disease biomarkers in patients with obstructive sleep apnea–hypopnea syndrome (OSAS), and the mean plasma levels of Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) in patients with severe OSAS were significantly higher than those in the control group. In addition, Aβ42, Aβ40, t-tau, and p-tau were significantly associated with indicators of OSAS, MiniMental State examination scale scores, and Epworth Sleepiness Scale scores. Cognitive decline in patients with OSAS may be existed in this population, which could be partly explained by repeated night hypoxia. Increased daytime sleepiness should be improved by appropriate treatment for OSAS, which would lead to prevent progression of cognitive impairment. I have some concerns about their study. First, the authors did not cite a reference by Bu et al., which examined the association between the chronic intermittent hypoxia and Aβ in OSAS patients [2]. The mean serum levels of Aβ40, Aβ42, and total Aβ levels in patients with OSAS were significantly higher than those in the control group. In addition, these biomarkers were positively associated with the apnea–hypopnea index, the oxygen desaturation index, and the mean and lowest oxyhemoglobin saturations. Furthermore, the OSAS patients exhibited a significant increase of serum p-tau 181 levels. They speculated that chronic intermittent hypoxia and increased Aβ levels would contribute to the pathogenesis of Alzheimer’s disease. They measured serum, not plasma, samples and the number of samples was limited. I think that intervention study may be needed to verify a causal relationship of OSAS and subsequent risk of cognitive impairment and Alzheimer’s disease. Second, the authors also cited a review by Bubu et al., who summarized reports examining OSA and cognitive impairment/Alzheimer’s disease, including biomarkers. Continuous positive airway pressure treatment for OSAS may be effective in improving cognition, and there is a link between OSAS and biomarkers of neurodegeneration in any generation. Unfortunately, there is a lack of enough information regarding dose–response relationship including severity and duration of OSAS and subsequent risk of cognitive impairment and Alzheimer’s disease by adjusting many confounders and interactions. Further studies are required for conducting a high-quality meta-analysis. Finally, Nakamura et al. reported that the clinical use of blood-based amyloid-β biomarkers has not been established [4]. This means that the agreement of amyloid-β positronemission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid with blood-based amyloid-β biomarkers is not satisfactory. They developed a new system of immunoprecipitation coupled with mass spectrometry for the measurement of high-performance plasma amyloid-β biomarkers. The ability of amyloid-β precursor protein (APP)669–711/amyloid-β (Aβ)1–42 and Aβ1-40/ Aβ1-42 ratios, and their composites were used to predict individual brain amyloid-β status by amyloid-β-PET imaging. The composite biomarker showed high performance of predictive ability by receiver-operating characteristics curve analysis, and these biomarkers were significantly correlated with brain amyloid-β-PET burden and levels of Aβ1-42 in cerebrospinal fluid. Although many measurement kits for This comment refers to the article available online at https:// doi. org/ 10. 1007/ s0040502005948-2.