Objective To explore diagnostic value of the immune intensity of platelet ?-amyloid precursor protein(APP) and isoforms proportion for Alzheimer's disease(AD).Methods The APP immune intensity of platelets was evaluated by flow cytometric detection and the isoforms proportion of APP130/APP106 was also detected by Western Blot analysis in 31 AD cases, 22 vascular dementia (VD) patients , 28 neural degeneration patients and 30 healthy elders.Results There was no significant difference of APP immunity in the each group. The ratio of APP130/APP106 was significantly lower in the AD group compared with the groups VD, degenerative disorder and healthy elders(all P

Objective To investigate SIAH′s role in α-synuclein degradation, formation of Lewy bodies and neuronal death. Methods Proliferative activity of PC12 cells was measures by MTT assay after treatment with MPP and Rapamycin. Western Blot was applied determine the protein expression of LC3-Ⅱ, E1, SIAH-1, P53 and α-synucleinto. PCR was applied to measure protein related mRNA levels. Immunofluorescent techniques were used to detect the distribution of α-synuclein, SIAH-1 and LC3 in cells after SIAH antibody processing. Results MPP+ treatment increased α-synuclein, E1 expression and SIAH-1 activity, however, LC3-Ⅱ, P53 and α-synuclein protein levels decreased significantly. Anti-SIAH-1 antibody treatment reversed this trend, with E1 significantly increased. Rapamycin treatment reduced SIAH-1 and α-synuclein levels in the MPP+ group. SIAH-1 antibody significantly decreased the positive immuno-stain of α-synuclein, SIAH-1 and LC3, suggesting loss of co-localization. Conclusions Anti-SIAH-1 supports the clearance of non-aggregated α-synuclein by the UPS. SIAH plays a key role in the pathogenesis of Parkinson′s disease and is a potential therapeutic target of neurodegenerative diseases.

OBJECTIVETo explore the mechanism underlying changes in microvascular reactivity in single- and double-transgenic mice.

METHODSPeripheral vascular reactivity to the vasodilators, acetylcholine and sodium nitroprusside, on perfused microvasculature of the hind footpad was investigated using nontransgenic mice, single-transgenic mice expressing the human APP-C100 (TgC100. WT or TgC100. V717F) and double-transgenic mice coexpressing human APP-C100 and human SOD(1) (G93A) genes.

RESULTSSingle TgC100 and double Tg mice C100/SOD(1) (G93A) at 2 - 3 months old showed a statistical decrease of 28% in blood flux compared to nontransgenic control mice. In addition, vasodilative responsiveness was markedly reduced to 34% in 8 - 9 months old TgC100 mice compared to control mice. There was no significant difference in the profile of vasodilative reaction between TgC100. WT and TgC100. V717F mice. TgC100 and double Tg mice also had higher levels of A beta peptide in plasma than nontransgenic mice (P < 0.01).

CONCLUSIONSThe present study suggests that the altered reactivity of the microvasculature may be mediated by circulating soluble A beta peptides. The mechanisms underlying the vasoactivity of circulating A beta in TgC100 and double Tg mice may involve both the endothelium and nonendothelium.

Acetylcholine ; pharmacology ; Amyloid beta-Peptides ; blood ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Blood Flow Velocity ; drug effects ; Hindlimb ; blood supply ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Mutation ; Nitroprusside ; pharmacology ; Peptide Fragments ; blood ; Superoxide Dismutase ; genetics ; metabolism ; Vasodilator Agents ; pharmacology