Research On Relationship Between The Processing Of Cholesterol And Alzheimer's Disease And Parkinson's Disease With Dementia

Part 1 Clinical study of serum cholesterol and lipid in ADObjective: The diagnosis of AD, as well as other diseases resulting in dementia, isstill a decision based on multiple sources of information that are consideredsimultaneously. Current evidence suggests that the vascular risk factors are importantin the pathogenesis of AD. An elevated total cholesterol level is considered a riskfactor in epidemiologic studies. The cholesterol influences the processing of amyloidprecursor protein (APP). Most of studies suggest that the serum total cholesterol levelis decreased, but a few elevated. So to investigate the changes of serum lipid andcholesterol of AD in western China, we study the outcomes of serum lipid andcholesterol of AD who live in Tianjin.Methods: Serum concentrations of lipid and cholesterol in 69 patients with AD and55 normal controls were detected and compared.Results:①The level of serum cholesterol in AD group was higher than those ofnormal control group (t=5.423, P=0.000).②The level of serum cholesterol in femaleAD group was higher than those of normal female control group (t=6.314, P=0.000).③The level of serum HDL in femaleAD group was higher than those of normalfemale control group (t=2.598, P=0.012).Conclusion:The level of serum cholesterol was elevated in female AD, at the sametime, the level of serum HDL was decreased.Part 2 Research on relationship between gene APOE and CYP46polymorphis:m and AD, PDD. PDObjective: The most potent risk factor is the presence of the apolipoprotein 84(APOEε4) allele. Of its 3 formsε2,ε3, and 84 only the 84 allele increases thelikelihood of developing AD. The lifetime risk of AD for an individual without the 84allele is approximately 9％whereas the lifetime risk of AD for an individual carryingat least one 84 allele is 29％. While representing a substantial risk of AD, the 84 genotype is not sufficiently specific or sensitive for the diagnosis of AD to allow itsuse as a diagnostic test. There have been conflicting reports of association of APOEpolymorphism with dementia in Parkinson disease (PD).There are few studies on therelationship in Chinese PDD and APOE. To determine the relationship betweenAPOE polymorphisms and Chinese PD with dementia (PDD), we have planned thisstudy. The gene CYP46 was considered another gene which has relationship with theprocessing of lipid except the gene APOE. So we have evaluated the association ofthe polymorphism in CYP46 gene with AD,PDD and PD in Chinese Han population.Methods: The polymorphisms in APOE and CYP46 gene were detected by genechip technique in 60 patients with AD,68 patients with PD,53 patients with PDD and56 controls.Results:①The distributions of APOE and CYP46 genotypes followed the law ofHardy-Weinberg equilibrium.②The allele of ApoEε3 was most common, andgenotype ofε3/3 was most seen inChinese Han population.③The ApoE e4 allelefrequency was significantly higher in AD and in PDD as compared to that in thenormal population(P＜0.05). The ApoE e2 allele frequency was significantly lower inpatients than in the normal control.④The age and sex-adjusted OR for the risk of ADin carriers of ApoE e4 allelewas 4.909. The age and sex-adjusted OR for the risk ofPDD in carriers of ApoE e4 allele was 3.086.⑤Our data showed that the distributionof CYP46 genotypes was significantly different in patients with AD,PDD and PD ascompared with controls. The presence of the genotype C/C was higher in AD andPDD patients compared to controls.⑥There are no relationship between the alleles ofCYP46 and AD,PDD,PD.Conclusion:①The genotype of ApoEε3/3 was most seen in Chinese Hanpopulation in tianjin.②The ApoE e4 allele frequency was significantly high inChinese AD and PDD in tianjin.③The ApoEε4 allele increases the likelihood ofdeveloping AD and PDD.④The presence of the genotype C/C was higher in AD andPDD patients compared to controls.⑤There are no relationship between the alleles of CYP46 and AD,PDD,PD.Part 3 the research on platelet APPr in AD and HCObjective: Alzheimer disease is a progressive neurodegenerative disease,characterised by a progressive cognitive and memory decline. From aneuropathological point of view, Alzheimer disease is defined by the presence ofcharacteristic lesions, i.e. mature senile plaques, neurofibrillary tangles (NFTs) andamyloid angiopathy. In particular, accumulation of the amyloid beta-peptide in thebrain parenchyma and vasculature is an invariant event in the pathogenesis of bothsporadic and familial Alzheimer cases. Amyloid beta-peptide originates from a largerprecursor, the amyloid precursor protein (APP) ubiquitously expressed. Among thedifferent peripheral cells expressing APP forms, platelets are particularly interestingsince they show concentrations of its isoforms equivalent to those found in brain.Moreover, a number of laboratories independently described alterations in APPmetabolism/concentration in platelets of Alzheimer patients when compared to controlsubjects matched for demographic characteristics. These observations defined theframe of our work aimed to investigate if a correlation between levels of platelet APPforms and Alzheimer disease could be detected. Recent studies have suggested thatcholesterol might play a role in the pathophysiology of AD by modulating Abetaproduction. Aim of this study was to evaluate the relationship between serumcholesterol levels and platelet APP processing.Methods: To test the AD and HC specificity of reduced platelet APP ratios, wequantitated respectively these APPs in sixteen male controls. APP ratios weredetermined using Western blotting with m22C11 monoclonal antibody and digitalscanning of autoradiographs.Results:①The ratio between the intensity of the 110-kd and 120- to 130-kd APPisoforms was significantly lower in the AD group compared with controls(t=19.448,P=0.000).②The ratio between the intensity of the 110-kd and 120- to130-kd APP isoforms was significantly lower in the HC group compared with controls (t=-41.611,P=0.000).Conelusion:①The APP processing in platelets of patients with Chinese AD isdifferent from that of control subjects in tianjin.②The pattern of platelet APPisoforms is altered in patients with HC.③APPr could be considered as a marker ofthe progression of AD.