Screening GGC repeat expansion in the NOTCH2NLC in early‐onset dementia: The Longitudinal Study of Early Onset Dementia and Family Members (LEAF) Study
Seung‐yeon Lee, Takeshi Mizuguchi, Hee Jin Kim, Young‐Eun Kim, Cho Hanna, Won‐Joo Kim, Gha‐Hyun Lee, Ahro Kim, Ji‐Yun Park, Eun Joo Chung, Hyemin Jang, Na‐Yeon Jung, Sun Min Lee, Sang Won Seo, Seong‐Ho Koh, Henrik Zetterberg, Liana G. Apostolova, Naomichi Matsumoto, So Young Moon, Eun‐Joo Kim,Abstract
BACKGROUND
Neuronal intranuclear inclusion disease (NIID) is neurodegenerative disorder caused by GGC repeat expansion in NOTCH2NLC . Given its frequency in young East Asian adults and overlap with cognitive impairment in young adults, a key feature of early‐onset dementia (EOD), we screened NOTCH2NLC GGC repeat expansions in Korean patients with EOD.
METHODS
We screened NOTCH2NLC GGC repeat expansions in 410 Korean patients with EOD using repeat‐primed and amplicon length polymerase chain reaction. Plasma biomarkers in adult‐onset leukodystrophy were additionally measured using Simoa‐based ultrasensitive immunoassays.
RESULTS
GGC repeat expansions were not identified in early‐onset Alzheimer's disease (AD) or frontotemporal dementia (FTD), while four of eleven patients with adult‐onset leukodystrophy (36.3%) had abnormal expansions. Plasma neurofilament light chain (NfL) level was lower in NIID than in colony‐stimulating factor 1 receptor–related disorder.
DISCUSSION
These findings support recent arguments that the concept of NOTCH2NLC ‐related GGC repeat expansion disorder (NRED) should be reconsidered. Plasma NfL may be useful in differential diagnosis of adult‐onset leukodystrophy.