Related Experiment Video

Updated: May 29, 2026

Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
06:02

Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants

Published on: November 28, 2025

GFAP mutations, age at onset, and clinical subtypes in Alexander disease

M Prust1, J Wang, H Morizono

  • 1Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA.

Neurology
|September 16, 2011
PubMed
Abstract

Insights

Alexander disease (AxD) subtypes are defined by age at onset and GFAP mutation site, impacting clinical presentation and mortality. This study proposes two distinct AxD types based on statistical analysis of patient data.

Area of Science:

  • Neuroscience
  • Genetics
  • Rare Diseases

Background:

  • Alexander disease (AxD) is a rare astrogliopathy characterized by leukodystrophy on MRI.
  • AxD is caused by mutations in the glial fibrillary acidic protein (GFAP) gene.
  • Understanding AxD phenotypes and their correlation with genetic factors is crucial for diagnosis and management.

Purpose of the Study:

  • To characterize Alexander disease (AxD) phenotypes.
  • To determine correlations between age at onset (AAO) and GFAP genetic mutations.
  • To statistically define AxD subtypes based on clinical and genetic data.

Main Methods:

  • Analysis of 30 new and 185 previously reported AxD cases.
  • Statistical methods including Wilcoxon rank sum tests, survival analysis, and chi-squared tests.
  • Latent class analysis (LCA) to identify distinct AxD patient groups.

Main Results:

  • LCA identified two AxD classes: Type I (early onset, severe symptoms) and Type II (later onset, distinct neurological features).
  • Type I AxD showed a significantly higher mortality risk compared to Type II.
  • Specific GFAP mutations (R79, R239) were common and correlated with distinct clinical outcomes, with R239 associated with a more aggressive disease course.

Conclusions:

  • Age at onset and GFAP mutation site are key predictors of AxD phenotype and prognosis.
  • The study proposes revised AxD subtypes (Type I and Type II) based on statistically defined patient groups.
  • These findings enhance the understanding of AxD heterogeneity and guide clinical management.

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

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...
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,...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...