High sensitivity to carcinogens in the brain of a mouse model of Alzheimer's disease.
Cancer and Alzheimer's disease (AD) are commonly found among elderly patients. Chronic inflammation is the characteristic of both diseases. Amyloid-beta peptide is the main inducer of inflammation in AD. Moreover, chronic inflammation promotes cancer, suggesting that AD patients may be more prone to develop cancer than non-demented people. To test this hypothesis, we injected the carcinogen 20-methylcholanthrene in the brain of transgenic mice overexpressing the mutant forms of amyloid precursor protein (APP) and presenilin 1 (PS1), as a model of AD, and their wild-type (WT) littermates. Mutant mice developed tumors faster and with higher incidence than their WT counterparts. Expression of the inflammatory markers interleukin (IL)-1alpha, IL-1beta, IL-6, IP-10 and tumor necrosis factor-alpha (TNF-alpha) was measured in AD and WT mice of 3 and 12 months of age that had not been exposed to the carcinogen. These cytokines were elevated in older AD mice, indicating the existence of a highly inflammatory milieu in these animals. We also found elevated expression of a mutated form of p53 in older AD mice, suggesting an alternative mechanism for the predisposition of AD brains to develop brain tumors. Clinical studies reporting comorbidity of AD and brain cancer are needed to understand whether our observations hold true for humans.
Serrano
J
J
Department of Molecular, Cellular, and Developmental Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Fernández
A P
AP
Martínez-Murillo
R
R
Martínez
A
A
D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D002273:Carcinogens; D016207:Cytokines; D016159:Tumor Suppressor Protein p53