title: Genetic study of Sardinian patients with Alzheimer's disease.
abstract: We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the gamma-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Piscopo
authors.forename: Antonella
authors.initials: A
authors.lastname: Manfredi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Malvezzi-Campeggi
authors.forename: Alessio
authors.initials: A
authors.lastname: Crestini
authors.forename: Ornella
authors.initials: O
authors.lastname: Spadoni
authors.forename: Rossella
authors.initials: R
authors.lastname: Cherchi
authors.forename: Emiliano
authors.initials: E
authors.lastname: Deiana
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Piras
authors.forename: Annamaria
authors.initials: A
authors.lastname: Confaloni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D053764:Presenilin-1; D053766:Presenilin-2; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; C469349:PSENEN protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D053829:Amyloid Precursor Protein Secretases