Genetic Variation in the G720/G30 Gene Locus (DAOA) Influences the Occurrence of Psychotic Symptoms in Patients with Alzheimer's Disease

Article type: Research Article

Authors: Di Maria, Emilio^{a; b; *} | Bonvicini, Cristian^c | Bonomini, Cristina^d | Alberici, Antonella^e | Zanetti, Orazio^d | Gennarelli, Massimo^{c; f}

Affiliations: [a] Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova, Italy | [b] Laboratory of Genetics, Galliera Hospital, Genova, Italy | [c] Genetic Unit, I.R.C.C.S. “San Giovanni di Dio”, Fatebenefratelli, Brescia, Italy | [d] Alzheimer Unit, I.R.C.C.S. “San Giovanni di Dio”, Fatebenefratelli, Brescia, Italy | [e] Clinica Neurologica, Biology and Genetics Division, University of Brescia, Italy | [f] Department of Biomedical Sciences and Biotechnologies, Biology and Genetics Division, University of Brescia, Italy

Correspondence: [*] Corresponding author: Emilio Di Maria, M.D., Ph.D., Department of Neuroscience, Ophthalmology and Genetics, University of Genova, and Laboratory of Genetics, Galliera Hospital, Genova, Italy, c/o Genetica Medica, Galliera Hospital, Via Volta, 6, 16128 Genova, Italy. Tel.: +39 0105634368; Fax: +39 01057481222; E-mail: [email protected].

Note: [] Communicated by Alessandro Serretti

Abstract: The occurrence of neuropsychiatric symptoms in patients with Alzheimer's disease hampers the clinical management and exacerbates the burden for caregivers. To what extent psychotic symptoms are genetically determined and which are the genes involved has to be established. We tested the hypothesis that the occurrence of delusions and hallucinations in AD is associated with variations in the G72/DAOA gene, which is supposed to play a key role in the glutamate pathway regulated through the NMDA receptors. A panel of single nucleotide polymorphisms were genotyped in a cohort of 185 Alzheimer's disease patients. The analysis demonstrated a nominally significant association (p< 0.05) with one single nucleotide polymorphism (rs2153674). In addition, multivariate regression showed that the rs2153674 genotype accounts for up to 15% of the variance in delusions severity, as assessed by using the Neuropsychiatric Inventory. If the results from the present study will be replicated, the glutamate hypothesis could be invoked to explain the occurrence of psychosis in neurodegenerative disorders.

Keywords: Association study, Alzheimer's disease, behavioral and psychological symptoms in dementia (BPSD), d-serine amino acid oxidase activator (DAOA), G72/G30, neuropsychiatric symptoms (NPS), psychotic symptoms

DOI: 10.3233/JAD-2009-1194

Journal: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 953-960, 2009