Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor
- 1 September 1992
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 359 (6390) , 64-67
- https://doi.org/10.1038/359064a0
Abstract
A PATHOLOGICAL hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of amyloid fibrils is β/A4 amyloid protein1,2, which can be generated by the aberrant processing of a large membrane-bound glycoprotein, the β/A4 amyloid protein precursor (APP)3. To test whether overexpression of APP generates abnormally processed derivatives that affect the viability of neurons, we stably transfected full-length human APP complementary DNA into murine embryonal carcinoma P19 cells. These cells differentiate into post-mitotic neurons and astrocytes after exposure to retinoic acid4–6. When differentiation of the APP cDN A-transfected P19 cells was induced, all neurons showed severe degenerative changes and disappeared within a few days. The degenerating neurons contained large amounts of APP derivatives that were truncated at the amino terminus and encompassed the entire β/A4 domain. These results suggest that post-mitotic neurons are vulnerable to overexpressed APP, which undergoes aberrant processing to generate potentially amyloidogenic fragments.Keywords
This publication has 27 references indexed in Scilit:
- Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril proteinPublished by Elsevier ,2004
- Processing of the Amyloid Protein Precursor to Potentially Amyloidogenic DerivativesScience, 1992
- Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicityBiochemical and Biophysical Research Communications, 1992
- A novel brain-specific mRNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cellsBiochemical and Biophysical Research Communications, 1991
- Neural differentiation-associated generation of microglia-like phagocytes in murine embryonal carcinoma cell lineDevelopmental Brain Research, 1991
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991
- Neural differentiation increases expression of Alzheimer amyloid protein precursor gene in murine embryonal carcinoma cellsBiochemical and Biophysical Research Communications, 1990
- The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjectsExperimental Neurology, 1989
- Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursorBiochemical and Biophysical Research Communications, 1989
- Functional expression of cloned cDNA encoding the α-subunit of adenylate cyclase-stimulating G-proteinFEBS Letters, 1987