Cytoskeleton derangement in brain of patients with Down syndrome, Alzheimer's disease and Pick's disease.

Although cytoskeleton derangement has been reported in brain of patients with neurodegenerative disorders, basic information on integral constituents forming this network including stoichiometric composition is missing. It was therefore the aim of the study to qualitatively and quantitatively evaluate individual proteins of the three major classes representing the cytoskeleton of human brain. Cytoskeleton proteins beta-actin (betaA), alpha-actinin (Act), tubulin beta-III (betaIII), microtubule associated protein 1 (MAP1), neurofilaments NF-L, NF-M and NF-H and neuron specific enolase (NSE), a marker for neuronal density, were determined by immunoblotting. Brain samples (frontal cortex) of controls (CO), patients with Down Syndrome (DS), Alzheimer's disease (AD) and Pick's disease (PD) were used for the study. In DS brain betaIII, NF-H and NF-M, in AD brain NF-M and NF-H and in PD brain NF-L, NF-M and NF-H were significantly reduced. Stoichiometry of cytoskeleton proteins in control brain revealed the following relations: betaA:Act:betaIII:MAP1:NF-L:NF-M:NF-H = 1.0:0.8:3.8:2.4:3.2:2.2. This stoichiometrical ratios were aberrant in DS, AD and PD with the main outcome that ratios of members of the neurocytoskeleton (betaIII, NF's) in relation to betaA were remarkably decreased. This finding confirms data of decreased neuronal density using NSE in DS and AD. We propose stoichiometry of cytoskeleton elements in normal brain and confirm and extend knowledge on cytoskeleton defects in neurodegenerative diseases. The finding of significantly decreased individual elements may well lead to or represent disassembly of the neurocytoskeleton observed in neurodegenerative diseases.