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

Donna M. Wilcock, Amyn Mohammed Rojiani, Arnon Rosenthal, Sangeetha Subbarao, Melissa J. Freeman, Marcia N. Gordon, Dave Morgan

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

Background: Anti-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. Methods: We 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. Results: After 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. Conclusions: The 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.

Original languageEnglish (US)
Article number24
JournalJournal of Neuroinflammation
Volume1
DOIs
StatePublished - Dec 8 2004
Externally publishedYes

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Passive Immunization
Amyloid Plaques
Amyloid
Immunotherapy
Transgenic Mice
Blood Vessels
Anti-Idiotypic Antibodies
Cerebral Amyloid Angiopathy
Adoptive Transfer
Water
Memory Disorders
Alzheimer Disease
Therapeutics
Clinical Trials
Learning
Hemorrhage
Injections
Brain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

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. / Wilcock, Donna M.; Rojiani, Amyn Mohammed; Rosenthal, Arnon; Subbarao, Sangeetha; Freeman, Melissa J.; Gordon, Marcia N.; Morgan, Dave.

In: Journal of Neuroinflammation, Vol. 1, 24, 08.12.2004.

Research output: Contribution to journalArticle

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