意大利利古里亚市老年痴呆症患者早期和晚发性阿尔茨海默病遗传危险因素的筛选

Title:Screening of Early and Late Onset Alzheimer’s Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy

Volume: 12 Issue: 8

Author(s): Raffaele Ferrari, Michela Ferrara, Anwar Alinani, Roger Brian Sutton, Francesco Famà, Agnese Picco, Guido Rodriguez, Flavio Nobili and Parastoo Momeni

Affiliation:

关键词: EOAD，性别，基因分型，LOAD，种群特异性，风险因素，测序。

摘要: Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer’s disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer’s and non-Alzheimer’s forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalenceof AD in the femalepopulation compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area. 

Cite this article as:

Ferrari Raffaele, Ferrara Michela, Alinani Anwar, Brian Sutton Roger, Famà Francesco, Picco Agnese, Rodriguez Guido, Nobili Flavio and Momeni Parastoo, Screening of Early and Late Onset Alzheimer’s Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy, Current Alzheimer Research 2015; 12 (8) . https://dx.doi.org/10.2174/1567205012666150710114751