Search

Recent studies have reported a genetic association between the 73 G/A polymorphism within exon 1 of the cystatin C gene and Alzheimer's disease (AD) with conflicting results. To further investigate the proposed association and to clarify the role of CST3 as risk factor for AD, we analyzed the genotype and allele frequency distribution of CST3 G73A and apolipoprotein (ApoE) gene polymorphisms in 243 Italian patients with AD and 186 controls. Patients with AD were consecutively collected among the outpatients from the Neurology Department at the University of Florence. All 429 subjects were genotyped for CST3 and ApoE polymorphisms. After stratification according to age, the GG frequency resulted slightly higher in younger (<65 years) cases, but far from statistically significant. There was also no evidence of a statistical interaction between CST3 and ApoE polymorphisms. In conclusion, our data suggest that the CST3 genetic variant is not a susceptibility factor in AD, nor mitigate the effect of the ApoE varepsilon4 allele in the risk of developing AD.

A recent study has shown that a genetic variation in the Cathepsin D (catD) gene is a major risk factor for the development of Alzheimer's disease (AD). CatD is an intracellular aspartyl protease involved in neurodegeneration. A C-->T (Ala-->Val) transition at position 224 has been associated with altered intracellular maturation. Recently, a significant overrepresentation of the T allele of the catD gene in AD patients compared with controls was reported. However, this finding has not yet been confirmed. We analyzed the distribution of catD and apolipoprotein E polymorphisms in Italian patients with sporadic and familial AD (FAD). Our studies revealed that the distribution of catD polymorphism did not differ in AD and FAD patients and controls. Thus, our data do not support a role for the catD gene as a genetic risk factor in the development of AD.

A 5-bp deletion and a Val1000 polymorphism at the alpha(2)-macroglobulin (A2M) gene have recently been reported to be associated with late onset Alzheimer's disease (AD). As recently it has been suggested that the effect of the A2M gene on AD susceptibility may be limited to certain populations or families, we analyzed the segregation of A2M and apolipoprotein E polymorphisms in Italian sporadic and familial AD. We analyzed the two polymorphisms in a total of 346 subjects including 98 controls by polymerase chain reaction-restriction fragment length polymorphism method. Our data do not confirm these associations, in particular we found a significant decrease of the deletion allele in AD with respect to controls. Our data do not support a role for the A2M gene as genetic risk factor for AD.

Numerous studies have provided evidence for a genetic association of the Apolipoprotein E (ApoE) epsilon4 allele and late onset familial and sporadic Alzheimer's disease (AD). Clinical observations show that a proportion of schizophrenic patients may suffer from severe cognitive impairment. That could reflect a particular clinical aspect of this mental disorder or a common, yet unknown, neurodegenerative mechanism. We analysed the ApoE gene polymorphism in a sample of 69 Italian patients with schizophrenia, 140 AD patients and 121 controls. In schizophrenic patients, the distribution of ApoE genotypes does not significantly differ from that of controls. No effect of the ApoE genotype on age of onset was found. The frequency of ApoE alleles in Italian schizophrenic patients is comparable with control values, suggesting that ApoE polymorphism does not represent a risk factor for schizophrenia.

Normal pressure hydrocephalus (NPH) is characterized by dementia, gait disorders and urinary incontinence. Apolipoprotein E (ApoE) epsilon4 allele has been associated with severity of dementia in Alzheimer's disease (AD) and in other forms of dementia. Moreover, homozygosity of the A allele of the alpha1-antichymotrypsin (ACT) gene and of allele 1 of the presenilin-1 (PS-1) gene was associated with an increased risk for late onset AD. We analyzed the distribution of ApoE, ACT and PS-1 genotypes and the corresponding allele frequencies in 13 NPH patients. No differences were found in ACT and PS-1 polymorphism distributions in the patients studied with respect to the control group. An increased ApoE epsilon4 allele frequency was observed in NPH patients with respect to controls, thus suggesting that epsilon4 allele may also be involved in the pathogenesis of the disease.

Our purpose was to test the dopamine D2 receptor gene (DRD2), the tyrosine hydroxylase (TH) gene and the monoamino oxydase A (MAO-A) gene for linkage to schizophrenia and bipolar disorders. We have analyzed seven Italian families with schizophrenia and four families with bipolar disorders for a total of 68 individuals; 32 individuals were affected. Diagnoses were made using the structured clinical interview Schedule for Affective Disorders and Schizophrenia, Lifetime version (SADS-L). The results of our study provide no evidence of linkage between alleles at D2 dopamine receptor loci and schizophrenia or bipolar disorders. The markers TH gene and MAO-A gene give slightly positive or negative results suggesting the utility of further analysis on more informative families.