GRN Variant rs5848 Reduces Plasma and Brain Levels of Granulin in Alzheimer's Disease Patients

Article type: Short Communication

Authors: Kämäläinen, Anna^{a; 1} | Viswanathan, Jayashree^{a; 1} | Natunen, Teemu^a | Helisalmi, Seppo^a | Kauppinen, Tarja^a | Pikkarainen, Maria^a | Pursiheimo, Juha-Pekka^b | Alafuzoff, Irina^c | Kivipelto, Miia^{a; d; e} | Haapasalo, Annakaisa^a | Soininen, Hilkka^{a; f} | Herukka, Sanna-Kaisa^{a; f} | Hiltunen, Mikko^{a; *}

Affiliations: [a] Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland | [b] Turku Centre for Biotechnology, University of Turku, Turku, Finland | [c] Department of Immunology, Genetics and Pathology, Uppsala University and Uppsala University Hospital, Uppsala, Sweden | [d] Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden | [e] Karolinska Institutet Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden | [f] Department of Neurology, Kuopio University Hospital, Kuopio, Finland

Correspondence: [*] Correspondence to: Mikko Hiltunen, PhD, Institute of Clinical Medicine – Neurology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Tel.: +358 40 355 2014; Fax: +358 17 162 048; E-mail: [email protected].

Note: [1] These authors contributed equally.

Abstract: Genetic variants in the granulin (GRN) gene have been shown to increase the risk of Alzheimer's disease (AD). Here, we report that the A allele of rs5848 in GRN reduces plasma granulin levels in a dose-dependent manner in a clinically-defined AD sample cohort. Similarly, the mRNA levels of granulin were decreased with respect to A allele of rs5848 in the inferior temporal cortex of neuropathologically confirmed AD patients. Our findings suggest that the A allele of rs5848 is functionally relevant by reducing the expression of granulin.

Keywords: Alzheimer's disease, granulin, GRN, microRNA, plasma, rs5848, temporal cortex

DOI: 10.3233/JAD-2012-120946

Journal: Journal of Alzheimer's Disease, vol. 33, no. 1, pp. 23-27, 2013