C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment
Cacace, Rita × Van Cauwenberghe, Caroline Bettens, Karolien Gijselinck, Ilse van der Zee, Julie Engelborghs, Sebastiaan Vandenbulcke, Mathieu Van Dongen, Jasper Bäumer, Veerle Dillen, Lubina Mattheijssens, Maria Peeters, Karin Cruts, Marc Vandenberghe, Rik De Deyn, Peter P Van Broeckhoven, Christine Sleegers, Kristel #
Neurobiology of Aging vol:34 issue:6 pages:1712.e1-7
C9orf72 GC 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 GC pathogenic repeat expansions in Flanders-Belgian patients with clinical AD or mild cognitive impairment (MCI). In addition, we studied the effect of non-pathogenic GC 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 GC 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.