Objective: Here we present the first human neuropathology following immunization with Ab (AN-1792). Amyloid b-peptide (Ab) plays a key role in the pathogenesis of Alzheimer’s disease (AD). Immunization with Ab in a transgenic mouse model of AD reduces both age-related accumulation of Ab in the brain and associated cognitive impairment. The crucial question is whether Ab immunotherapy influences human AD pathology.
Materials and Methods: Macroscopic examination of the brain, neuritic plaques, neurofibrillary tangles, and neuropil threads were identified in the cerebral neocortex by modified Bielshowsky, thioflavine S, and tau and bAPP immunostaining.
Design: Post mortem examination of a case involved in the Ab immunization trial of AN1792 using immunohistochemical techniques to further our understanding of the effects of this form of therapy on the neuropathology of AD.
Results: The findings are highly unusual in that:
1) despite diagnostic neuropathological features of AD, many brain regions contain very few Ab plaques;
2) areas of brain devoid of plaques contain Ab immunoreactive microglia;
3) despite the sparseness of Ab plaques there is extensive and severe cerebral amyloid angiopathy; and
4) there is an extensive T lymphocyte infiltrate in the leptomeninges and a sparse infiltrate in the cerebral cortex not normally seen in AD.
Conclusion: These findings strongly resemble the changes seen in transgenic mice immunized with Ab and suggest the possibility that the immune response generated against the peptide elicited clearance of Ab plaques in this patient. The T lymphocyte meningoencephalitis is likely to correspond to the uncommon side effect seen in some other patients who received AN-1792.
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