Clinical Neuroscience

[Lack of associations between CLU and PICALM gene polymorphisms and Alzheimer’s disease in a Turkish population]

SEN Aysu1, ARSLAN Mehtap2, ERDAL Emin Mehmet3, AY Izci Ozlem3, YILMAZ Gorucu Senay3, KURT Erhan2, ARPACI Baki1

MARCH 25, 2015

Clinical Neuroscience - 2015;68(03-04)

[Background and purpose - To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer’s disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. Methods - One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and “No BPSD” and “BPSD”. Results - The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the “No BPSD” and the “BPSD” groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the “No BPSD” patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. Conclusion - This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.]


  1. Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Department of Neurology, Istanbul, Turkey
  2. Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Department of Psychiatry, Istanbul, Turkey
  3. Mersin University, Faculty of Medicine, Department of Medical Biology and Genetics, Mersin, Turkey



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[Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative disorder of the central nervous system (CNS). There are nine drugs available in Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to reduce the activity of the disease, from which seven can be used as first line therapies. We have approximately 20 years of experience with the interferon b-1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the patients using one of the first line drugs, the disease remains active, that we call break-through disease. The reasons for break-through disease could be the insufficient adherence and compliance, the appearance of neutralizing antibodies or the high activity of the disease. One of the oral immunomodulating drugs for MS, teriflunomide, was registered in Europe in 2013. Because of the anti-proliferative and anti-inflammatory effect of teriflunomide, it can be used for the reduction of the disease activity in the relapsing-remitting course of MS. The effect of teriflunomide was proved in one Phase II. and four Phase III. (TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to demonstrate in two consecutive placebo-controlled phase 3 clinical trials that significantly reduces the relapse rate (31.5% and 36.3%) and in both studies significantly reduces the sustained disability progression (29.8% and 31.5%) moreover delays the appearance of the clinically definitive MS in patients with clinically isolated syndrome (CIS). According to the TENERE study there were no significant differences observed between teriflunomide 14 mg and IFNb-1a s.c. in time to failure and annualized relapse rate but the treatment satisfaction domains of global satisfaction, side-effects and convenience were significantly improved with teriflunomide compared with s.c. IFNb-1a. ]

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