The Study On The Relationship Between The Inflammatory Factors And Parkinson Disease And Alzheimer Disease

[Background] Parkinson disease (PD) and Alzheimer disease(AD) are the most common neurodegenerative disorders in the aged. The cause and the pathogenic mechanisms of PD and AD are unclear. There are some similar in clinical characteristics between PD and AD. Cognitive impairment even dementia often happen in PD, while Parkinsonism signs are showed in AD. Whether there are some relationship between the pathogenic mechanisms of PD and AD are becoming the focus.In the present study, There is definite link between inflammatory factors and PD and AD. There are many activated microglia around the degenerative neuron in animal models and pathologic autopsy. These microglia release many inflammatory factors including IL-1β,IL-6, TNF-α, ACT. These inflammatory factors mainly exist in nigrostriatal system in PD patients and amyloid protein and senile plaque in AD patients. These reaches demonstrate the inflammatory factors that activated microglia release may be attend the course that PD patients and AD patients'neuron degeneration. Our research use serum inflammatory factors level and genetic polymorphisms to presume the pathogenesis and cause of PD and AD.Accumulation of the amyloid beta-peptide in the brain is an invariant event in the pathogenesis of Alzheimer that inflammatory factors attented in.Amyloid beta-peptide originates from a larger precursor,the amyloid precursor protein(APP)ubiquitously expressed.95%APP of circulation are exist in platelets. Just like the changes in the brain of AD patients, The amyloid way of APP is activated in the platelets of AD patients.It make Aβaggradate to SP.M22C11 monoclonal antibody can close N ternal of APP, We use it as immune print. APP can be cut up two segments(120-130kDa and 110kDa)by m22C11.Many studies find,APP ratios in AD patients are decreased compare to controls.[Objectives] To investigate the association of serum IL-1β, IL-6, TNF-α, ACT levels and IL-6, ACT genetic polymorphisms with PD and AD patients in Tianjin Han population, in order to explore the pathogenesis and mechanism and direct the treatment of PD and AD. At the same time, We test APPr in platelets in AD patients,and anlysis the effection of imflammatory protein.lt will provide new way to dignosis AD.[Methods] We conducted a case-control study.150 cases PD patients and 100 cases AD patients were enrolled and given detailed clinical investigations, physical examinations. Use H-Y scale describe the state of PD patients. To AD patients performed tests including mini-mental state examination (MMSE), clock drawing test(CDT) and activity of daily life living (ADL).100 cases healthy controls came from healthy physical examination center in the General Hospital. The polymorphisms in ApoE,IL-6 and ACT gene were detected by gene chip technique in 150 patients with PD,100 patients with AD and 100 healthy controls. Levels of serum IL-1β, IL-6, TNF-α, ACT of 40 cases in each group were detected by ELISA. The correlations between these factors and the incidence of PD or AD were analyzed respectively. APPr of 40 AD patients and 30 healthy controls were detected by Western Blotting.The data was computed by SPSS 11.5.[Results]1. PD group,AD group and healthy controls were similar in age and sex, subgroups were matched by age, sex, disease duration.2. The serum IL-1βlevels in the normal group,AD group and PD group had significant deference (P< 0.05). Serum IL-1βlevel of AD and PD group increased as compared with normal group, the difference was statistically significant (P<0.05).3. The serum IL-6 levels in the normal group,AD group and PD group had significant deference (P<0.05). Serum IL-6 level of AD and PD group increased as compared with normal group, the difference was statistically significant (P<0.05). Serum IL-6 level in AD increased as compared with PD group, the difference had not statistically significant (P>0.05).4. The serum TNF-a levels in the normal group,AD group and PD group had significant deference (P<0.05). Serum TNF-αlevel of AD and PD group increased as compared with normal group, the difference was statistically significant (P<0.05). Serum TNF-a level in AD increased as compared with PD group, the difference had not statistically significant (P>0.05), which indicated TNF-a may be involve in the pathogenic mechanisms of AD and PD. 5. The serum ACT levels in the normal group,AD group and PD group had significant deference (P<0.05). Serum ACT level of AD and PD group increased as compared with normal group, the difference was statistically significant (P<0.05). Serum ACT level in AD increased as compared with PD group, the difference had not statistically significant (P>0.05), which indicated ACT may be involve in the pathogenic mechanisms of AD and PD.6. We analysis the relation that the alteration of serum IL-1β,IL-6,TNF-α,ACT levels and the MMSE scores, correlation analysis showed serum IL-6 and ACT levels were negative association with MMSE scores (r=-0.951, r=-0.598,P<0.05). The serum levels of IL-1βand TNF-αhad not association with MMSE scores (P>0.05).7. We analysis the relation that the alteration of serum IL-1β,IL-6,TNF-α,ACT levels and the H-Y scores, correlation analysis showed serum IL-1βand ACT levels were positive association with H-Y scores (r=0.686, r=0.874,P<0.05). The serum levels of IL-6 and TNF-a had not association with H-Y scores (P>0.05).8. The distributions of ApoE,IL-6 and ACT genotypes followed the law of Hardy-Weinberg equilibrium. The allele of ApoEε3 was most common and genotype of s3/3 was most seen in Chinese Han population. The ApoE s4 frequency was significantly higher in AD as compared to that in the nomal population (P<0.05). The age and sex-adjusted OR for the risk of AD in carriers of ApoE s4 allele was 3.143.9. Our data showed that the distribution of IL-6 genotypes was no significantly different in patients with AD,PD as compared with controls.10. The distributions of ACT genotypes was significantly different in AD,PD group with in controls group. The presence of the genotype A/A was higher in PD group, OR for the risk of PD in carriers of ACT A/A was 2.756. The patients carriers both ACT A/A and ApoEε4 in AD groups had significantly different as compared with nomal groups (P<0.05).11. APPr was significantly different in AD group with in controls group.The groups of AD with serum ACT level> 70mg/dl and with serum ACT level< 60mg/dl had significantly different as compared with nomal groups (P<0.05),The groups of AD with serum ACT level> 70mg/dl and AD with serum ACT level<60mg/dl had no significantly different (P=0.125)。[Conclusions]1. The serum levels of inflammatory factors (IL-1β,IL-6,TNF-α,ACT) has increased in AD and PD patients. That may be the dangerous factors to AD and PD. The serum levels of IL-6 and ACT was association with cognitive impairment in AD patients. The serum levels of IL-1βand ACT was association with motor disturbance in PD patients.2. ApoE genes4 allele carrier is a risk factor of AD patients and has no association with PD patients. There is no directly correlated between IL-6 gene and AD or PD.ACT A/A genotype has association with PD. ACT gene and ApoE gene may have a synergetic role on the occurrence of AD.3. Platelets APPr has decreased in AD patients compare with nomal control group.4. Different serum level of APPr of AD patients has no significantly differents compare with nomal control group.ACT have no effect to the metabolize of APP.5. Platelets APPr may become marker to dignosis AD.