title: Intracellular Aβ-oligomers and early inflammation in a model of Alzheimer's disease.
abstract: Lifelong use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to diminish the incidence of Alzheimer's disease (AD), suggesting a key role of inflammation in early stages of the pathology. While amyloid plaque-associated inflammation has been extensively studied in human and animal models, little is known about the inflammatory process prior to plaque deposition, i.e., in preclinical stages of AD. In this study we investigated microglial and neuronal inflammatory markers in preplaque transgenic McGill-Thy1-APP mice. We found evidence that prior to plaque deposition classical markers of microglial activation such as major histocompatibility complex class II (MHC-II), inducible nitric oxide synthase (i-NOS), and CD40 are already upregulated in the hippocampus of transgenic mice. Microglial cells from transgenic mice in the preplaque stage displayed intermediately activated morphology and appeared to be recruited toward intracellular amyloid-β peptide (Aβ)-oligomer burdened neurons. The inducible, neuron-specific cyclooxygenase 2 (COX-2) enzyme was found to be upregulated and specifically expressed by neurons in close relationship with Aβ-bearing cells, at this early stage of the AD-like pathology. Our study suggests that neuroinflammation might be one of the earliest pathological responses to intracellular accumulation of Aβ-oligomers.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ferretti
authors.forename: Martin A
authors.initials: MA
authors.lastname: Bruno
authors.forename: Adriana
authors.initials: A
authors.lastname: Ducatenzeiler
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007424:Intracellular Fluid / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides