Cortical Frontoparietal Network Dysfunction in CHMP2B-Frontotemporal Dementia

Abstract

A rare cause of inherited frontotemporal dementia (FTD) is a mutation in the CHMP2B gene on chromosome 3 leading to the autosomal dominantly inherited FTD (CHMP2B-FTD). Since CHMP2B-FTD is clinically well-characterized, and patients show a distinct pattern of executive dysfunction, the condition offers possible insight in the early electroencephalographic (EEG) changes in the cortical networks. Specifically, EEG microstate analysis parses the EEG signals into topographies believed to represent discrete network activations. We investigated the EEG dynamics in patients with symptomatic CHMP2B-FTD (n = 5) as well as pre-symptomatic mutation carriers (n = 5) compared to non-carrier family members (n = 6). The data was parsed into four archetypal microstates and global power was calculated. A trend was found for lower occurrence in microstate D in CHMP2B-FTD (p-value = 0.177, F-value = 2.036). Patients with recent symptom onset (<1 year) showed an increased duration of microstate D, whereas patients who had been symptomatic for longer periods (>2 years) showed decreased duration. Patients with CHMP2B-FTD present with executive dysfunction, and microstate D has previously been shown to be associated with the fronto-parietal network. The biphasic pattern may represent the pathophysiological changes in brain dynamics during neurodegeneration, which may apply to other neurodegenerative diseases.

Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review

“…Among them, the most common is the C9orf72 gene mutation, accounting for about 25% of cases [ 18 ]. Other reported mutations include those of valosin containing protein ( VCP ), charged multivesicular body protein 2B ( CHMP2B ) , TAR DNA-binding protein of 43 kDa( TDP-43 ), fused in sarcoma( FUS ), integral membrane protein 2B [ 19 , 20 ], TANK-binding kinase 1 [ 21 ], and TATA box-binding protein [ 22 ]. The gene mutation analysis of our patient showed mutations in the ALS pathogenesis-associated GRN gene c.1352C > T (p.P451L) and ErbB4 gene c.256 T > C (p.Y86H).…”