Related Experiment Video

Updated: Jun 5, 2026

An Improved Method to Isolate Mitochondrial Contact Sites
07:55

An Improved Method to Isolate Mitochondrial Contact Sites

Published on: June 16, 2023

Frontotemporal dementia caused by CHMP2B mutations

A M Isaacs1, P Johannsen, I Holm

  • 1Department of Neurodegenerative Disease, VCL Institute of Neurology, Queen Square, London, UK. la.isaacs@prion.ucl.ac.uk

Current Alzheimer Research
|January 13, 2011
PubMed

Insights

Mutations in the CHMP2B gene are a rare cause of frontotemporal dementia (FTD). These genetic alterations lead to truncated proteins, impacting cellular degradation pathways and causing FTD.

Area of Science:

  • Neurogenetics
  • Cellular Biology
  • Neurodegenerative Diseases

Background:

  • CHMP2B mutations represent a rare genetic cause of autosomal dominant frontotemporal dementia (FTD).
  • The most studied form is frontotemporal dementia linked to chromosome 3 (FTD-3), prevalent in a large Danish family.
  • Additional CHMP2B mutations have been identified in familial FTD cases, including an unrelated Belgian patient.

Purpose of the Study:

  • To review recent advances in understanding the molecular mechanisms of CHMP2B truncation mutations.
  • To examine the impact of these mutations on vesicular fusion, endosome-lysosome pathways, and autophagy.
  • To consolidate current knowledge on the clinical, neuroimaging, and neuropathological features of CHMP2B-related FTD.

Main Methods:

  • Literature review of studies on CHMP2B mutations in FTD.
  • Analysis of molecular effects of C-terminal CHMP2B truncations on cellular pathways.
  • Compilation of clinical data, brain imaging, and neuropathological findings.

Main Results:

  • CHMP2B mutations result in C-terminal protein truncations.
  • These truncations affect vesicular fusion, endosome-lysosome function, and autophagy.
  • Clinical features, imaging, and neuropathology of CHMP2B-related FTD are reviewed.

Conclusions:

  • CHMP2B mutations are implicated in specific forms of familial frontotemporal dementia.
  • Understanding the molecular pathology is crucial for FTD research.
  • Further investigation into CHMP2B missense mutations in FTD and motor neuron disease is warranted.

More Related Videos

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging09:37

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Published on: July 14, 2016

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains12:28

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains

Published on: June 3, 2020

Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Dementia l: Introduction01:22

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
Dementia01:30

Dementia

Dementia is a collective term for cognitive disorders primarily affecting memory, thinking, and reasoning. It is not a specific disease but a syndrome, with Alzheimer's disease being the most common cause, accounting for approximately 60-80% of cases. Other types include vascular dementia, Lewy body dementia, and frontotemporal dementia. Dementia affects millions worldwide, particularly older adults, though it is not a normal part of aging.
The progression of dementia is generally gradual.