iTRAQ-Based Proteomic Analysis of APP Transgenic Mouse Urine Exosomes.

Alzheimer's disease (AD) is a common dementia disease in the elderly. To get a better understanding of the pathophysiology, we performed a proteomic analysis of the urine exosomes (U-exo) in AD model mice (J20). The polymer precipitation method was used to isolate U-exo from the urine of 3-month-old J20 and wild-type (WT) mice. Neuron-derived exosome (N-exo) was isolated from U-exo by immunoprecipitation. iTRAQ-based MALDI TOF MS/MS was used for proteomic analysis. The results showed that compared to WT, the levels of 61 and 92 proteins were increased in the J20 U-exo and N-exo, respectively. Gene ontology enrichment analysis demonstrated that the sphingolipid catabolic process, ceramide catabolic process, membrane lipid catabolic process, Aß clearance, and Aß metabolic process were highly enriched in U-exo and N-exo. Among these, Asah1 was shown to be the key protein in lipid metabolism, and clusterin, ApoE, neprilysin, and ACE were related to Aß metabolism and clearance. Furthermore, protein-protein interaction analysis identified four protein complexes where clusterin and ApoE participated as partner proteins. Thus, J20 U-exo and N-exo contain proteins related to lipid- and Aß-metabolism in the early stages of AD, providing a new insight into the underlying pathological mechanism of early AD.

Effect of Multimorbidity on Fragility Fractures in Community-Dwelling Older Adults: Shimane CoHRE Study.

Fragility fractures (FFxs), which are a common musculoskeletal injury in older adults, is associated with an increased frequency of falls. Both FFxs and falls may result from drugs, habits, and co-occurring diseases. We aimed to evaluate the effects of various diseases on the risk of FFx. This retrospective study included 1420 individuals aged ≥60 years. We evaluated the history of clinical FFx and diseases using a detailed questionnaire and a health examination. The risk of comorbidities was assessed using the Age-Adjusted Charlson Comorbidity (AAC) Index. We performed binary logistic regression analysis to determine the risk of FFx and falls after adjusting for covariates. In elderly men, the incidence of FFx positively correlated with rheumatoid arthritis and parent's hip fracture. For elderly women, the incidence of FFx positively correlated with rheumatoid arthritis and antihypertensive drugs but was inversely associated with dyslipidemia and antilipidemic drugs. The FFX risk of older adults with an AAC Index ≥6 was higher than those with an AAC Index of 1-3. In addition, the AAC Index and falls were independently and strongly associated with a higher risk of FFx. Taken together, multimorbidity increases the risk of clinical FFx independent of falls in the community-dwelling elderly population.

Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer's Disease Mouse Model: A Role of Ethanolamine Plasmalogen.

Plasmalogens are alkenyl-acyl glycerophospholipids and decreased in post-mortem Alzheimer's disease (AD) brains. The aim of this study is to investigate the time-dependent changes of plasmalogens in the hippocampus of an AD model mouse (J20). Plasmalogen levels at 3, 6, 9, 12 and 15 months were analyzed by liquid-chromatography-targeted-multiplexed-selected-reaction-monitoring-tandem-mass-spectrometry (LC-SRM/MS). Reactive oxygen species (ROS) levels were evaluated using dichlorofluorescein diacetate (DCF-DA). Plasmalogen synthesizing enzyme glycerone-phosphate O-acyltransferase (GNPAT) and late endosome marker Rab7 levels were quantified by Western blotting. GNPAT localization, changes of neuronal and glial cell numbers were evaluated by immunostaining. Compared to wild-type mice (WT), total plasmalogen-ethanolamine, but not plasmalogen-choline levels, were increased at 9 months and subsequently decreased at 15 months in J20 mice. A principal component analysis of plasmalogen-ethanolamine species could separate WT and J20 mice both at 9 and 15 months. Both GNPAT and Rab7 protein were increased in J20 mice at 9 months, whereas GNPAT was decreased at 15 months. ROS levels were increased in J20 mice except for 9 months. Our results suggest that increased plasmalogen-ethanolamine could counteract ROS levels and contribute to the phagocytosis process in J20 mice at 9 months. Such results might indicate a transient protective response of plasmalogen-ethanolamine in AD conditions.