Previous studies demonstrate that patients with sleep disorders are at risk of developing Alzheimer's disease (AD), with the mechanism unknown. It is suggested that acute sleep deprivation induces an increase of amyloid-β (Aβ), the major pathological agent in AD, in the cerebrospinal fluid (CSF). In the present study, we recruited 23 patients with chronic insomnia aged between 46 to 67 years and 23 healthy controls aged between 43 to 67 years. We investigated the CSF levels of Aβ and tau, another pathological hallmark in the AD pathogenesis. We found that CSF Aβ42 levels were significantly increased in insomnia patients. However, no significant difference was found in Aβ40, total tau (t-Tau), and phosphorylated tau (p-Tau) between the two groups. Furthermore, we found that CSF Aβ40 and Aβ42 levels are significantly correlated with the sleep quality, as reflected by the Pittsburgh Sleep Quality Index (PSQI) scores. But no significant correlation was found in CSF t-Tau and p-Tau levels with PSQI. Our results indicate that chronic sleep disorders may induce the disruption of Aβ metabolism in the brain, thus increase the risk for developing AD.

Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

Brain amyloid-␤ (A␤) deposition is a hallmark to define Alzheimer's disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11 C-Pittsburgh compound (PiB)-PET and blood A␤ levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18 F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of A␤ 42 , A␤ 40 , and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma A␤ 42 /A␤ 40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95%CI: 0.66-0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.

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Background A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery. Methods We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice. Results We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice. Conclusion Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.