The New Gasotransmitter Hydrogen Sulfide And Other Biomarkers In Alzheimer's Disease And Vascular Dementia

Objective:To clarify the role of endogenous H2S, Hcy, NO and CRP in the pathogenesis of AD and VD. The plasma concentrations of H2S, Hcy, NO and CRP were measured in 31 patients with Alzheimer's disease(AD), 28 patients with vascular dementia(VD), 20 patients with cerebrovascular diseases(CVD) and 23 normal controls (NC).Methods:All patients, including 31 patients with AD, 28 patients with VD, and 20 patients with CVD, were recruited from the neurology department, The First Affiliated Hospital of Chongqing Medical University from 2005 until 2006.Assessments and diagnosis: (1)AD group:patients fulfilled NINCDS- ADRDA criteria for probable'AD'and Hachinski Ischemic Score (HIS)<4.(2)VD group: patients fulfilled NINDS/AIREN criteria VD and had a HIS>7. (3)CVD group:patients have a history of cerebral vascular disease (had two weeks of the history at least ),focal neurologic symptoms or signs, and the evidences of CVD using CT scan or MRI,In addtion,no cognitive disturbance was found.(4)NC group:healthy prople with machted age, gender were enrolled as controls. They had no history of neurologic diseases, no family history of stroke or dementia and no mental problems,Mini Mental State Examination(MMSE), Activity of Daily Living Scale (ADL), Hachinski Ischemic Score (HIS) and Hamilton's depression scale (HRSD) were performed in all patients and controls. The diagnosis was confirmed by two neurologists. The severity of AD and VD was evaluated according to Global Deterioration Scale (GDS).The plasma levels of Hcy, H2S, NO and CRP were measured in all the objects by Fluorescence Polarization Immunoassay, sensitive sulpher electrode, Nitrate/Nitrite colorimetric assay and immunoturbidimetry respectively.Results:①the plasma level of H2S was significantly lower in the patients with AD(34.03±6.78μmol/L), or with VD(36.37±5.21μmol/L), or with CVD (37.49±6.83μmol/L) than in NC(44.92±6.53μmol/L)(P<0.01). However, there was no significant difference in the subgroups of patients. Through rank correlation analysis, the severity of AD was negative correlation with the plasma concentration of H2S, in other words, there was a tendency that plasma level of H2S decreased gradually following the aggravation of AD,We learned that there was not a linear correlation between plasma H2S level and the scores of MMSE.②the plasma level of Hcy was significantly higher in the patients with AD (14.02±2.95μmol/L), or with VD(16.03±6.07μmol/L), or with CVD (14.42±4.95μmol/L) than in NC (9.79±2.51μmol/L) (P<0.01), However, there was no significant difference in subgroups of patients(P >0.05).Through rank correlation analysis, the severity of AD or VD was positive correlation with the plasma concentration of Hcy. We learned that there was a negative correlation between plasma Hcy level and the scores of MMSE in patients with VD but not in patient with AD.③the plasma level of NO was significantly lower in the patients with AD(36.06±13.92μmol/L), or with VD(41.11±18.77μmol/L), or with CVD(43.10±19.08μmol/L) than in NC(60.17±19.77μmol/L) (P < 0.01), However, there was no significant difference in subgroups of patients(P>0.05). Through rank correlation analysis, the severity of AD was negative correlation with NO, in other words, there was a tendency that plasma NO decreased gradually following the aggravation of AD,We learned that there was not a correlation between plasma NO level and the scores of MMSE.④The plasma level of CRP was higher in the cases with VD(4.38±3.46 mg/l) and CVD(2.62±1.77mg/l) than in the normal controls (1.11±1.30mg/l). Through spearman correlation analysis, the severity of AD was positive correlation with CRP, in other words there was a tendency that plasma CRP level increased gradually following the aggravation of VD. ⑤Pearson Correlations analysis between plasma concentrations of Hcy, H2S, NO and CRP in AD, VD, CVD and NC: there was a negative correlation between plasma concentrations of Hcy and hydrogen sulfide in patients with AD, Moreover there was also no correlation between other biomarkers in NC, AD, VD and CVD.Conclusions:①Gasotransmitter H2S is involved in the pathogenesis of AD, VD and CVD, and its alteration in level may be associated with the severity of AD.②Plasma levels of Hcy was a risk factor for the development of dementia as well as for CVD, plasma Hcy alteration may be connected with the severity of dementia.③Gasotransmitter NO may be interact with H2S and involved in the pathogenesis of AD, VD and CVD.④CRP, a blood inflammatory marker, and its alteration in plasma level is connected with the severity of VD. However, CRP can not be a predict factor of AD.