Amyloid- peptide (A) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with A in a transgenic mouse model of AD reduces both age-related accumulation of A in the brain1 and associated cognitive impairment2,
3. Here we present the first analysis of human neuropathology after immunization with A (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few A plaques; (ii) those areas of cortex that were devoid of A plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, A-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)−(iii) strongly resemble the changes seen after A immunotherapy in mouse models of AD1,
2,
3,
4,
5,
6 and suggest that the immune response generated against the peptide elicited clearance of A plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7−9).
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