Meyer-Luehmann, Melanie; Mora, J. Rodrigo; Mielke, Matthew; Spires-Jones, Tara L.; Calignon, Alix de; Andrian, Ulrich H. von; Hyman, Bradley T.:
T cell mediated cerebral hemorrhages and microhemorrhages during passive A beta immunization in APPPS1 transgenic mice.
In: Molecular Neurodegeneration
Background: Immunization against amyloid-beta (A beta), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated A beta in transgenic mice. In a clinical trial of A beta immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization. Results: To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti A beta IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas. Conclusions: Our results indicate that vaccination can lead to A beta and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.