GRN variant rs5848 reduces plasma and brain levels of granulin in Alzheimer's disease patients.
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.
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Anna
A
Kämäläinen
Jayashree
J
Viswanathan
Teemu
T
Natunen
Seppo
S
Helisalmi
Tarja
T
Kauppinen
Maria
M
Pikkarainen
Juha-Pekka
JP
Pursiheimo
Irina
I
Alafuzoff
Miia
M
Kivipelto
Annakaisa
A
Haapasalo
Hilkka
H
Soininen
Sanna-Kaisa
SK
Herukka
Mikko
M
Hiltunen
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D000077153:Progranulins
D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins