Impaired Mitochondrial and Glycolytic Functions in Peripheral Blood Leukocytes of Alzheimer’s Disease

Recent failures of the trials targeting amyloid to treat Alzheimer’s disease (AD) are prompting scientists to explore other pathological pathways. Brains of AD patients have been noted to have impaired mitochondrial function. It has not yet been determined if AD is caused by a systemic defect in cellular bioenergetics. To determine the cellular bioenergetics, we compared the Oxygen Consumption Rate (OCR – indicating oxygen dependent respiration) and Extra Cellular Acidification Rate (ECAR – indicating glycolytic function) in leukocytes of collected blood samples of Alzheimer’s and non-dementia patients. Methods: After IRB approval and consents, blood samples from each clinically diagnosed Alzheimer’s and age matched normal subjects were collected. Immediately after collection the blood samples were analyzed using Agilent Seahorse XFe/XF Analyzer as per protocol by manufacturer. Results: Impaired mitochondrial and glycolytic functions were noted in Alzheimer’s patients as compared to normal subjects. OCR was significantly lower in Alzheimer’s patients. A lower rate of respiration was noted both at basal as well as maximal respiration. Reduced spare respiration capacity was also noted in response to the stressors. Similarly reduced ECAR and reduced glycolytic reserve was also noted in Alzheimer’s patients, indicating impaired oxygen independent mitochondrial respiration. Discussion: This pilot study demonstrates that there is an impaired mitochondrial and glycolytic function in the peripheral blood cells. This indicates towards a systemic nature of the disease and a potential future bio-marker. Further studies should be planned in this direction.

OPERATING (FUNCTIONAL) CHARACTERISTICS OF APARTMENT PRESSURE REGULATORS AND ENERGY SAVING

The reasons of loss of water in apartment buildings due to excessive pressures (pressure) of water appliances. It is shown that the practical implementation of the regulatory requirements on the application of the apartment pressure regulators revealed its signifi cant systemic defect - worded compulsory hardware requirements are minimal, but not exhaustive, which eliminates the positive eff ect of its application. Defi nes the ways of improving the design of apartment pressure regulators and the mandatory requirements of the safety of buildings and structures.

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Young adult Hodgkin lymphoma (YAHL) is associated clinically with altered immunity, including a systemic defect in cell-mediated responses. There is strong evidence of a genetic contribution to risk, so we hypothesized that heritable alterations in cytokine production associated with Th1 function may contribute to susceptibility. We identified twin pairs in whom at least one member had YAHL and measured interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-γ (IFN-γ) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in 90 case-twins, 84 of their disease-free twins (unaffected cotwins), and 90 matched controls. Mean difference and mean percentage difference in cytokine levels between case-twins and controls, and unaffected cotwins and controls were determined using analysis of covariance. YAHL case-twins and their unaffected cotwins had IL-12 levels that were 60.6% (P = .002) and 49% (P = .04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in case-twins (P = .049), but not unaffected cotwins (P = .57), compared with controls. Differences in IFN-γ levels were not statistically significant in either comparison. An IL-12 polymorphism known to regulate expression was associated with a 2.8-fold (P = .03) increase in YAHL risk. Thus, both case-twins and their unaffected cotwins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility.