Abstract
BackgroundImmunization against amyloid-β (Aβ), 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 Aβ in transgenic mice. In a clinical trial of Aβ 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.ResultsTo 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 Aβ 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.ConclusionsOur results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.
Highlights
Immunization against amyloid-b (Ab), 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 Ab in transgenic mice
In order to investigate the T cell inflammatory response, developed as a consequence of active immunization in human Alzheimer’s patients, we immunized T-green fluorescent protein (GFP) mice with Ab42 followed by adoptive transfer of these fluorescently labeled T cells into mice that are transgenic for human APP
In vivo multiphoton microscopy for visualization and tracking of T cells in the brain of APPPS1 transgenic mice did not detect any transferred T cells during 1 hour in vivo imaging sessions (Additional File 1, Figure S1 A,B) green T cells were readily found at post mortem examination, most prominently in the spleens of the mice (Additional File 1, Figure S1 D)
Summary
Immunization against amyloid-b (Ab), 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 Ab in transgenic mice. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, and a powerful immune response involving activated T cells probably underlying the negative effects of the immunization. Mice that have been genetically altered so that they have quantities of Ab in their brains have plaque pathology similar to that seen in Alzheimer’s patients [2,3,4] Studies of immunizing these APP transgenic mice with the Ab peptide led to the exciting discovery that the immune system can prevent plaque formation and even reverse some of the damage by producing antibodies to Ab [5]. The clearance of plaques can lead to normalization of the neuritic processes and dystrophies surrounding plaques, suggesting an astonishing degree of plasticity in the adult brain, and potential for recovery [11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
