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- Title
Expression of the cytokine leukemia inhibitory factor and pro-apoptotic insulin-like growth factor binding protein-3 in Alzheimer's disease.
- Authors
Rensink, Annemieke A.; Gellekink, Henkjan; Otte-Höller, Irene; ten Donkelaar, Hans J.; de Waal, Robert M.; Verbeek, Marcel M.; Kremer, Berry
- Abstract
Amyloid-β (Aβ) deposition in cerebral blood vessel walls is one of the key features of Alzheimer's disease (AD). Aβ1–40 carrying the "Dutch" mutation (DAβ1–40) induces rapid degeneration of cultured human brain pericytes (HBP). To study the mechanisms of this Aβ-induced toxicity, a comparative cDNA expression array was performed to detect differential gene expression of Aβ-treated versus untreated HBP. Messenger RNA expression of leukemia inhibitory factor (LIF) and insulin-like growth factor binding protein 3 (IGFBP-3) was increased in DAβ1–40-treated HBP, whereas early growth response factor-1 (Egr-1) expression was decreased. Corresponding protein expression was investigated in AD and control brains. In all AD cases examined, LIF expression was observed in senile plaques and cerebral amyloid angiopathy, whereas IGFBP-3 expression in these lesions was only observed in a subset of cases. LIF and IGFBP-3 were also expressed in neurofibrillary tangles, as well as in neurons in AD and control brains. Egr-1 was predominantly expressed in astrocytes. Given its known involvement in both neuronal and immune responses to injury, the cytokine LIF may be a mediator of the inflammatory reaction seen in AD. IGFBP-3 is known to inhibit cell proliferation and induce apoptosis and may therefore contribute to neuronal degeneration in AD.
- Subjects
HYPOGLYCEMIC agents; GLYCOPROTEINS; EUGENICS; APOPTOSIS; CYTOKINES; MESSENGER RNA; LEUKEMIA
- Publication
Acta Neuropathologica, 2002, Vol 104, Issue 5, p525
- ISSN
0001-6322
- Publication type
Article
- DOI
10.1007/s00401-002-0585-x