Genetics and Expression Analysis of the Specificity Protein 4 Gene (SP4) in Patients with Alzheimer's Disease and Frontotemporal Lobar Degeneration

Article type: Research Article

Authors: Villa, Chiara^a | Ghezzi, Laura^a | Fenoglio, Chiara^a | Clerici, Francesca^b | Marcone, Alessandra^c | Benussi, Luisa^d | Ghidoni, Roberta^e | Gallone, Salvatore^f | Serpente, Maria^a | Cantoni, Claudia^a | Ridolfi, Elisa^a | Bonsi, Rossana^a | Cerami, Chiara^{c; g} | Cappa, Stefano^{c; g} | Binetti, Giuliano^d | Franceschi, Massimo^h | Rainero, Innocenzo^f | Mariani, Claudio^b | Bresolin, Nereo^a | Scarpini, Elio^{a; 1} | Galimberti, Daniela^{a; 1; *}

Affiliations: [a] Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy | [b] Center for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy | [c] Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy | [d] NeuroBioGen-Lab-Memory Clinic, IRCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [e] Proteomics Unit, IRCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [f] Department of Neuroscience, University of Turin, Turin, Italy | [g] Vita-Salute San Raffaele University, Milan, Italy | [h] IRCCS Multimedica, Milan, Italy

Correspondence: [*] Correspondence to: Daniela Galimberti, Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy. Tel.: +39 025503847; Fax: +39 0255036580; E-mail: daniela.galimberti@unimi.it.

Note: [1] These authors contributed equally to this work.

Abstract: Transcription factor Sp4 (Specificity protein 4) levels are increased in the brain of patients with Alzheimer's disease (AD), and Sp4 colocalizes with neurofibrillary tangles. Moreover, SP4 is a susceptibility gene for bipolar disorder and schizophrenia, which share many clinical features with frontotemporal lobar degeneration (FTLD). The distribution of three tagging single nucleotide polymorphisms(SNPs)—rs9639379, rs10272006, and rs6461569—has been determined in a population of 352 patients diagnosed clinically with AD, 290 patients with FTLD, and 341 age-matched controls. Expression analysis of SP4 was performed in peripheral blood mononuclear cells (PBMC). No significant differences in either allelic or genotypic frequency of the three SNPs were found (p > 0.05), even stratifying according to gender and to the apolipoprotein E status. Significantly increased SP4 relative expression levels were observed in PBMC from patients with AD as compared with controls (7.132 ± 1.301 versus 3.396 ± 0.829, p < 0.050) and a similar trend was shown in patients with FTLD compared with controls (6.525 ± 1.500 versus 3.396 ± 0.829, p = 0.073). According to these results, SP4 gene does not act as a susceptibility factor either for AD or FTLD. However, Sp4 mRNA levels are upregulated in patients, possibly resulting in an aberrant expression of downstream target genes involved in the pathogenesis of both diseases.

Keywords: Alzheimer's disease, expression, frontotemporal lobar degeneration, risk factor, SP4, specificity protein 4

DOI: 10.3233/JAD-2012-120379

Journal: Journal of Alzheimer's Disease, vol. 31, no. 3, pp. 537-542, 2012