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Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

Authors
  • Wilcock, Donna M1
  • Rojiani, Amyn2
  • Rosenthal, Arnon3
  • Subbarao, Sangeetha3
  • Freeman, Melissa J1
  • Gordon, Marcia N1
  • Morgan, Dave1
  • 1 University of South Florida, Department of Pharmacology, Alzheimer's Research Laboratory, 12901 Bruce B Downs Blvd, Tampa, Florida, 33612, USA , Tampa
  • 2 University of South Florida, Department of Interdisciplinary Oncology, Alzheimer's Research Laboratory, 12901 Bruce B Downs Blvd, Tampa, Florida, 33612, USA , Tampa
  • 3 Rinat Neuroscience Corp., 3155 Porter Drive, Palo Alto, California, 94304, USA , Palo Alto
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 08, 2004
Volume
1
Issue
1
Identifiers
DOI: 10.1186/1742-2094-1-24
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundAnti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice.MethodsWe investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing.ResultsAfter 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy.ConclusionsThe cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage.

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