1. Centre for Research in Neurodegenerative Diseases, Departments of Medicine, Laboratory Medicine and Pathobiology, and Medical Biophysics, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, Ontario M5S 3H2, Canada
2. Nathan Kline Institute Center for Dementia Research, and New York University School of Medicine, 140 Old Orangeburg Road, Orangeburg, New York 10962, USA
3. Janssen Research Foundation, Turnhoutseweg, 30, B-2340 Beerse, Belgium
4. Departments of Medicine (Division of Neurology) and Pathology, Toronto Western Hospital, University Health Network , Toronto, Ontario M5S 1A8, Canada

Correspondence to: Correspondence and requests for materials should be addressed to P.H.StG.-H. (e-mail: Email: p.hyslop@utoronto.ca).

Abstract

Much evidence indicates that abnormal processing and extracellular deposition of amyloid- peptide (A), a proteolytic derivative of the -amyloid precursor protein (APP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A causes a marked reduction in burden of the brain amyloid^{2, 3}. Evidence that A immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A immunization reduces both deposition of cerebral fibrillar A and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A in the brain. This implies that either a 50% reduction in dense-cored A plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A species.

1. Centre for Research in Neurodegenerative Diseases, Departments of Medicine, Laboratory Medicine and Pathobiology, and Medical Biophysics, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, Ontario M5S 3H2, Canada
2. Nathan Kline Institute Center for Dementia Research, and New York University School of Medicine, 140 Old Orangeburg Road, Orangeburg, New York 10962, USA
3. Janssen Research Foundation, Turnhoutseweg, 30, B-2340 Beerse, Belgium
4. Departments of Medicine (Division of Neurology) and Pathology, Toronto Western Hospital, University Health Network , Toronto, Ontario M5S 1A8, Canada

Correspondence to: Correspondence and requests for materials should be addressed to P.H.StG.-H. (e-mail: Email: p.hyslop@utoronto.ca).