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Maria Teresa Ferretti'Neuroinflammation in Alzheimer's Disease: controversies and new insights '

Abstract :

Conflicting results have been reported in the literature concerning the role of neuroinflammation in Alzheimer's disease.
On one hand, prospective studies with anti-inflammatory drugs in patients with Alzheimer's disease have shown no effect, or even a worsening of the pathology. Based on those results, it appears that blocking inflammation is not a suitable therapeutic approach to cure Alzheimer's disease. On the other hand, epidemiological data demonstrated that life-long users of nonsteroidal anti-inflammatory drugs develop the disease with reduced frequency. Such evidence would rather suggest that the inhibition of inflammation in early stages is protective against the onset of the pathology later in life. The contradictory reports might be consistent with a biphasic involvement of inflammation in Alzheimer's disease: a latent, pre-clinical inflammatory process, which would facilitate the disease progression, followed by a later, plaque-associated inflammation, which would be mostly beneficial. This lecture will offer a critical overview of the clinical and preclinical data available on the role of neuroinflammation in Alzheimer's disease. The evidence supporting a biphasic role of inflammation in the progression of the pathology will be discussed. In particular, I will be presenting preliminary results generated at McGill University suggesting a pivotal role of microglial activation in pre-plaque stages of the disease.

Selected publications

Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of AD-like amyloid pathology. Ferretti MT, Allard S, Partridge V, Ducatenzeiler A, Cuello AC. J Neuroinflammation. 2012 Apr 2;9(1):62. [Epub ahead of print]

Intracellular Aβ-oligomers and early inflammation in a model of Alzheimer's disease. Ferretti MT, Bruno MA, Ducatenzeiler A, Klein WL, Cuello AC; Neurobiology of Aging, 2011 March 15 [Epub ahead of print]

Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment? Ferretti MT, Cuello AC. Curr Alzheimer Res. 2011 Mar;8(2):164-74.

Transgenic mice as a model of pre-clinical Alzheimer's Disease. Ferretti MT, Partridge V, Leon WC, Canneva F, Allard S, Arvanitis DN, Vercauteren F, Houle D, Ducatenzeiler A, Klein WL, Glabe CG, Szyf M, Cuello AC.;
Current Alzheimer Research, 2011 Feb;8(1):4-23.

Scientific focus :

Dr Ferretti graduated in Pharmaceutical Chemistry at the University of Cagliari, Italy, with a Master Thesis on the distribution of GDNF receptors in the human brain stem. In 2006 she started her doctoral studies in the Department of Pharmacology and Therapeutics at McGill University (Montreal, Canada), under the supervision of Prof. Claudio Cuello. Here she became involved in the characterization of novel rodent (mice and rats) transgenic models of Alzheimer's disease-like pathology. For her research, she has taken advantage of such transgenic models to document pathological events occurring in early, pre-symptomatic stages of Alzheimer's disease. Dr Ferretti's main interest is understanding the role of immune cells, in particular microglial cells, in the progression of the disease.

Since December 2011 she is a post-doctoral fellow at University of Zurich, in the group of Prof. Roger Nitsch, working on the immunological aspects of Alzheimer's disease.

Thierry Amédée