NR AODQ
AU Askanas,V.; Engel,W.K.
TI Phenotypic molecular similarities between inclusion-body myositis (IBM) muscle and Alzheimer and prion-disease brain
QU Journal of Neuropathology and Experimental Neurology 1996; 55(N5): 631 Nr. 106
PT Meeting Abstract
VT
IBM the most common progressive and debilitating muscle disease in aging persons. Pathologic hallmarks of IBM are vacuolated muscle fibers (VMFs) containing paired-helical filaments (PHFs) and congophilia. Recently, we have identified within the VMFs of IBM abnormal accumulations of: a) several "AIzheimer specific proteins" namely B-amyloid protein (AB), N- and C-epitopes of ß-amyloid precursor protein (BAPP), hyperphosphorylated tau, apolipoprotein E (ApoE), alpha1-antichymotrypsin, ubiquitin (UBI), and transforming growth factor beta; b) ßAPP mRNA; c) cellular prion protein (PrPc); and d) PrPc mRNA. IBM PHFs are similar to AD PHFs, i.e. both contain hyperphosphorylated tau (tau-P), ApoE, and UBI. Ultrastructural immunolocalization of proteins accumulated in IBM VMFs is shown below.
Structure Aß N-ßAPP C-ßAPP UBI Tau-P ApQE Prion
PHFs - - - + + + +
6-10 nm Filaments + - - + - +/- +
Amorphous Material + + + + - +/- +
Flocculo-membranous + + + + - +/- +
material
Striking similarity between cellular phenotypes of IBM muscle and Alzheimer and prion-disease brain may result from: 1) a cascade of similar pathogenic steps occurring in the muscle-fiber and the neuron but provoked by different etiologies; 2) multiple causes producing the upregulation of a common cellular gene, whose protein is a transcription factor for BAPP and/or PrPc; 3) a tie-specific intracellular aging change that may be a requisite enhancing mechanism.
IN Die Einschlußkörpermyositis ist durch vacuolisierte Muskelfasern und Akkumulationen verschiedener Alzheimer-Proteine, sowie des Prionproteins gekennzeichnet.
ZR 0 Zitate
AD Valerie Askanas* and W. King Engel*, Neuromuscular Center, USC School of Medicine, Los Angeles, CA
SP englisch
OR Prion-Krankheiten 1