Overexpression of the Neuritotrophic Cytokine S100β Precedes the Appearance of Neuritic β‐Amyloid Plaques in APPV717F Mice

• Published in: Journal of neurochemistry Vol. 74; no. 1; pp. 295 - 301
• Main Authors: Sheng, J. G., Mrak, R. E., Bales, K. R., Cordell, B., Paul, S. M., Jones, R. A., Woodward, S., Zhou, X. Q., McGinness, J. M., Griffin, W. S. T.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.01.2000; Blackwell
• Subjects: Aging; Alzheimer’s disease; APPV717F mice; Astrocytes; Biological and medical sciences; Cytokines; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Inflammation; Medical sciences; Neurology; PDAPP mice; S100^b protein; S100b protein; S100β; Transgenic mice; β‐Amyloid; β‐Amyloid precursor protein; Nervous system diseases; Senescence; Senile plate; Alzheimer disease; Neuroglia; Rodentia; Cytokine; Transgenic animal; Gene overexpression; Astrocyte; Amyloid precursor protein; Cerebral disorder; Vertebrata; Mammalia; Mouse; Central nervous system disease; Degenerative disease; Age
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0740295.x

: Homozygous APPV717F transgenic mice overexpress a human β‐amyloid precursor protein (βAPP) minigene encoding a familial Alzheimer’s disease mutation. These mice develop Alzheimer‐type neuritic β‐amyloid plaques surrounded by astrocytes. S100β is an astrocyte‐derived cytokine that promotes neurite growth and promotes excessive expression of βAPP. S100β overexpression in Alzheimer’s disease correlates with the proliferation of βAPP‐immunoreactive neurites in β‐amyloid plaques. We found age‐related increases in tissue levels of both βAPP and S100β mRNA in transgenic mice. Neuronal βAPP overexpression was found in cell somas in young mice, whereas older mice showed βAPP overexpression in dystrophic neurites in plaques. These age‐related changes were accompanied by progressive increases in S100β expression, as determined by S100β load (percent immunoreactive area). These increases were evident as early as 1 and 2 months of age, months before the appearance of β‐amyloid deposits in these mice. Such precocious astrocyte activation and S100β overexpression are similar to our earlier findings in Down’s syndrome. Accelerated age‐related overexpression of S100β may interact with age‐associated overexpression of mutant βAPP in transgenic mice to promote development of Alzheimer‐like neuropathological changes.