C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment.
C9orf72 G4C2 repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Its role in Alzheimer's disease (AD) is less clear. We assessed the prevalence of G4C2 pathogenic repeat expansions in Flanders-Belgian patients with clinical AD or mild cognitive impairment (MCI). In addition, we studied the effect of non-pathogenic G4C2 repeat length variability on susceptibility to AD, and on AD cerebrospinal fluid (CSF) biomarker levels. A pathogenic repeat expansion was identified in 5 of 1217 AD patients (frequency <1%). No pathogenic expansions were observed in patients with MCI (n = 200) or control individuals (n = 1119). Nonpathogenic repeat length variability was not associated with AD, risk of conversion to AD in MCI individuals, or CSF biomarker levels. We conclude that pathogenic C9orf72 G4C2 repeat expansions can be detected in clinical AD patients and could act as a contributor to AD pathogenesis. Non-pathogenic repeat length variability did not affect risk of AD or MCI, nor AD biomarker levels in CSF, indicating that C9orf72 is not a direct AD risk factor.
Department of Molecular Genetics, VIB, Antwerp, Belgium.
Rita
R
Cacace
Caroline
C
Van Cauwenberghe
Karolien
K
Bettens
Ilse
I
Gijselinck
Julie
J
van der Zee
Sebastiaan
S
Engelborghs
Mathieu
M
Vandenbulcke
Jasper
J
Van Dongen
Veerle
V
Bäumer
Lubina
L
Dillen
Maria
M
Mattheijssens
Karin
K
Peeters
Marc
M
Cruts
Rik
R
Vandenberghe
Peter P
PP
De Deyn
Christine
C
Van Broeckhoven
Kristel
K
Sleegers
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D001530:Belgium / Q000453:epidemiology; D000073885:C9orf72 Protein; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins