Gene mutations in inherited amyloidopathies of the nervous system.
Year: 1991
Type: article
Abstract: Three papers published in this issue of the Journal (Bakker et al. 1991; Hiltunen et al. 1991; Schellenberg et al. 1991a) involve gene mutations responsible for amyloidoses affecting the nervous system. All three of these amyloidopathies are inherited in an autosomally dominant manner and involve the extracellular accumulation of amyloid. Amyloid is a general term for deposits of insoluble proteinaceous debris possessing specific tinctorial properties. In two of these disorders-an inherited form of dementia of the Alzheimer type and Dutch hereditary cerebral hemorrhage with amyloidosis (HCHWA-D)-the amyloid beta protein precursor (APP) serves as the substrate for amyloid formation. In the third disorderfamilial amyloidosis of Finnish type (FAF) -the substrate for amyloid formation is the actin-binding protein, gelsolin. In each case, the production of large amounts of amyloid in different forms is associated with specific clinical symptoms, ultimately leading to death. The APP gene encodes a set of normal membraneassociated proteins which are ubiquitously distributed in most peripheral and central nervous system tissues (Goldgaber et al. 1987; Kang et al. 1987; Robakis et al. 1987; Tanzi et al. 1987a). The principle component of the amyloid cores found in senile plaques in patients with Alzheimer disease (AD) and Down syndrome (DS) and, to lesser extent, in normal elderly individuals, is the 39-43-amino-acid peptide termed OiA4 (Glenner and Wong 1984). 13A4 is also the chief constituent of cerebral vessel amyloid deposits found in patients with AD, DS, and HCHWA-D (Glenner and Wong 1984; Van Duinen et al. 1987). The com-
Source: Europe PMC (PubMed Central)
Author: R E Tanzi
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1648205852