title: The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patients.
abstract: Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n=321) and non-demented control (n=208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Italy, Psychiatric Department Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tumini
authors.forename: Elisa
authors.initials: E
authors.lastname: Porcellini
authors.forename: Martina
authors.initials: M
authors.lastname: Chiappelli
authors.forename: Chiara M
authors.initials: CM
authors.lastname: Conti
authors.forename: Alina
authors.initials: A
authors.lastname: Beraudi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poli
authors.forename: Francesco
authors.initials: F
authors.lastname: Caciagli
authors.forename: Robert
authors.initials: R
authors.lastname: Doyle
authors.forename: Pio
authors.initials: P
authors.lastname: Conti
authors.forename: Federico
authors.initials: F
authors.lastname: Licastro
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications*; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics*; D012307:Risk Factors; D012694:Serine / Q000235:genetics; D013997:Time Factors
chemical_list: D053327:Apolipoprotein E4; D012694:Serine; D011683:Purine-Nucleoside Phosphorylase; D005998:Glycine