Proteasomal dysfunction: a way to classify FTD subjects?

Abstract

FTD is the most common clinical manifestation of FTLD; therefore, our study will focus on this subtype. It is pathologically characterized by extensive heterogeneity on the microscopic level with tau', ubiquitin', TDP'43' or FUS'positive intraneuronal inclusions. Although, a classification scheme is currently used to subdivide FTD patients based on the expression of these markers, not all patients fit perfectly into this diagram. Fisher et al. found that out of eight FTD individuals studied, three were ubiquitin B+1 (UBB+1)'positive. UBB+1 is a marker for a dysfunctional proteasome system and expression of this protein has already been shown in tauopathies (e.g. AD) and polyglutamine disorders. A first objective is to compare the mutual relationship of the FTD markers. The main purpose is to improve the manner in which FTD cases are currently classified based on UBB+1 expression. We showed it is very hard to classify a FTD patient in the current known groups. The experiments demonstr