Intermediate-length CGG repeat expansion in NOTCH2NLC is associated with pathologically confirmed Alzheimer's disease

• Intermediate-length CGG repeat expansion in NOTCH2NLC was identified in AD brain • P62-positive intranuclear inclusions could co-exist with AD neuropathologic changes • The CGG repeat expansion in NOTCH2NLC is closely associated with AD Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pathologically, it is characterized by β-amyloid plaques and neurofibrillary tangles. There are several genes have been found to relate to AD, including the human-specific Notch2 N terminal-like C ( NOTCH2NLC ) gene. The CGG repeat expansion in NOTCH2NLC has been reported in clinically diagnosed AD patients. However, it has not been reported in pathologically confirmed AD cases. In this study, we detected the NOTCH2NLC CGG repeat expansion in pathologically confirmed AD brain samples by repeat-primed PCR (RP-PCR) and fluorescence amplicon length analysis PCR (AL-PCR). As a result, the intermediate-length CGG repeat expansion in NOTCH2NLC was validated in one out of 39 pathologically confirmed AD cases. Pathologically, p62 positive intranuclear inclusions were observed in wide brain areas, and most inclusions appeared to be presented in the glial cells. In summary, our study found that the intermediate-length CGG repeat expansion in NOTCH2NLC was associated with pathologically confirmed AD. The p62-positive intranuclear inclusions could co-exist with AD neuropathologic changes. These data suggest that the association of NOTCH2NLC CGG repeat expansion with AD may be stronger than in previous studies.