Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer's disease hippocampus

Abstract

Endosomal sorting complex required for transport (ESCRT)-III subunit charged multivesicular body protein 2B (CHMP2B) is involved in the degradation of proteins in the endocytic and autophagic pathways. Mutations in the CHMP2B gene are reportedly associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) characterised by accumulation of ubiquitinated protein aggregates in affected neurons, suggesting a relationship between protein accumulation and efficient autophagic degradation. This study investigated CHMP2B immunoreactivity in the hippocampus of patients with Alzheimer's disease (AD), revealing intense labeling of intraneuronal dot-like structures by antibody to CHMP2B. Since the morphological characteristics of these granular structures were compatible with those of granulovacuolar degeneration (GVD), a hallmark of AD pathology, immunohistochemical study using anti-CHMP2B antibody was performed using AD and control brain sections to investigate whether this antibody can be used as a GVD label. The number and percentage of hippocampal neurons with CHMP2B-positive granules were higher in AD cases and CHMP2B-positive granules corresponded to GVD. Anti-CHMP2B antibody detected a single 28-kDa band on Western blotting using control and AD specimens. This antibody clearly and intensely detected GVD over the hippocampus and entorhinal and transentorhinal cortices. These findings suggest that researchers will be able to use CHMP2B as a molecular label for studying GVD.