BackgroundMany studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE) in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem.Principal FindingsHere we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were ∼20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G1+G2 forms and not G4 tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF) and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer's disease (AD) patients compared to age and gender-matched controls. This increase correlates with an increase in the G1+G2 forms, the subset of AChE species which are increased in Alzheimer's brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer's plasma, attributed in part to AChE-T subunits common in brain and CSF.ConclusionPlasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.

Highlights A report of a young patient with COVID-19 presenting with an encephalitis syndrome mimicking acute demyelinating encephalomyelitis. The patient was successfully treated with immunoglobulins and cytokine blockade. Acute encephalitis amenable to immunomodulation could be a feature of COVID-19.

Some studies have determined that oxidative stress is a decisive factor in Alzheimer's disease (AD) and even suggested that it is present in the initial phase of mild cognitive impairment (MCI). The aim of our study was to investigate the process of oxidative stress by measuring the level of malondialdehyde (MDA), the specific activity of two peripheral antioxidant defenses (superoxide dismutase (SOD) and ceruloplasmin), and the level of copper in AD and MCI patients and compare those results with healthy subjects. The sample group consisted of 36 patients with AD, 18 patients with MCI, and 33 healthy aged subjects. Blood samples were obtained from each subject. A significantly higher copper level was found in patients with AD and MCI compared to the control group. The levels of MDA showed a similar trend and were higher in patients from the AD and MCI groups than in the control group. It was found that both studied parameters had positive correlation in the whole studied population (r = 0.340; p = 0.001). A stepwise logistic regression analysis was used to identify an optimal combination of these biomarkers. The optimal biomarker combinations were MDA and SOD with area under the curve of 0.803 (0.691-0.915, CI 95%, p < 0.001) for the diagnosis of AD. The optimal cutpoint yielded 88.0% Sensitivity and 70.0% Specificity. The biomarker combinations predicted AD and were markedly superior to individual biomarkers. Our findings support the hypothesis that oxidative stress might represent a sign of AD pathology and could be an early event in the progression of MCI to AD.

BackgroundThe disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of the amyloid precursor protein. This study assesses whether ADAM10 is present in cerebrospinal fluid (CSF), and whether it has potential as a biomarker for Alzheimer’s disease (AD).MethodsADAM10 was characterized in human CSF samples by immunoprecipitation and western blotting using antibodies specific for different domains of the protein and by ultracentrifugation in sucrose density gradients. Samples from AD patients (n = 20) and age-matched non-AD controls (n = 20) were characterized for classical CSF biomarkers, Aβ42, T-tau, or P-tau by ELISA, and assayed for soluble ADAM10 levels by western blotting.ResultsWe found that ADAM10 is present in human CSF as several distinct species: an immature form retaining the prodomain (proADAM10; ~ 80 kDa), a mature unprocessed full-length form (ADAM10f; ~ 55 kDa), and a truncated large soluble form released from the membrane (sADAM10; ~ 50 kDa). Fractionation by ultracentrifugation on sucrose density gradients showed that the ADAM10f and sADAM10 species form large complexes. Immunoblotting revealed a significant decrease in ADAM10f and sADAM10 in AD CSF compared to control CSF, while proADAM10 levels remained unaltered.ConclusionsSeveral forms of ADAM10 are present in CSF, mainly assembled as high-molecular weight complexes. The determination of the levels of mature forms of CSF-ADAM10 may be useful as a biomarker for AD.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1255-9) contains supplementary material, which is available to authorized users.