Brain, Vol. 126, No. 2, 285-291,
February 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg031
Vaccination with amyloid-ß peptide induces autoimmune encephalomyelitis in C57/BL6 mice
1 Neuroimmunology Unit and 2 Department of Pathology, San Raffaele Scientific Institute, 3 Department of Neurology, University Vita-Salute, San Raffaele Hospital, Milan and 4 Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Correspondence to: Dr Gianvito Martino, Neuroimmunology Unit – DIBIT, Department of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy E-mail: martino.gianvito{at}hsr.it
Recent experimental evidence shows that vaccination with amyloid-ß peptide (Aß) of transgenic mouse models of Alzheimer’s disease protects from the pathological accumulation of amyloid within the CNS. Phase I/II clinical trials of Aß vaccination in mild to moderate Alzheimer’s disease have been undertaken. Un expectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation. Here, we show that C57BL/6 mice immunized with Aß1–42 peptide develop an inflammatory disease of the CNS characterized by the presence both in the brain and spinal cord of perivenular inflammatory foci containing macrophages, T and B cells, and immunoglobulins. The experimental disease was observed only when pertussis toxin, an agent known to favour autoimmune processes, was co-administered. The immune-mediated CNS reaction was associated to Aß-induced CD4+ cells showing a Th1-type cytokine expression profile and to elevated levels of circulating anti-Aß immunoglobulins. Our results indicate that vaccination with Aß could determine, under certain circumstances, an aberrant autoimmune-type reaction to Aß resulting in a perivenular inflammatory encephalomyelitis.
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