title: Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy.
abstract: 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 prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Michela
authors.initials: M
authors.lastname: Ferrara
authors.forename: Anwar
authors.initials: A
authors.lastname: Alinani
authors.forename: Roger Brian
authors.initials: RB
authors.lastname: Sutton
authors.forename: Francesco
authors.initials: F
authors.lastname: Famà
authors.forename: Agnese
authors.initials: A
authors.lastname: Picco
authors.forename: Guido
authors.initials: G
authors.lastname: Rodriguez
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: Department of Internal Medicine 4C179/4B134-135, Texas Tech University Health Sciences Center, 3601 4th St. STOP 9410, Lubbock Texas 79430, USA. parastoo.momeni@ttuhsc.edu.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000235:genetics; D015331:Cohort Studies; D003704:Dementia / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D012307:Risk Factors