Absence of β-Amyloid Deposits After Immunization in Alzheimer Disease With Lewy Body Dementia

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Abstract
Objective To describe the neuropathological and biochemical findings of the brain examination of a patient enrolled in the AN-1792(QS-21) trial with an initial clinical diagnosis of Alzheimer disease (AD), in whom Lewy body variant was thereafter clinically diagnosed. Design A case report. Setting University memory clinic. Patient A 74-year-old woman with clinical features of probable AD. Intervention The patient received 2 injections of 225 μg of AN-1792 (β-amyloid [Aβ]) plus 50 μg of the adjuvant QS-21 at an interval of 4 weeks. The patient was an antibody responder with an IgG anti–AN-1792 antibody titer exceeding 10 000 and an IgM titer exceeding 3500. Maximum serum anti-Aβ titers were reached in 4.7 months. During the 3 following years, while the Mini-Mental State Examination score remained globally stable despite several confusional episodes, she developed clinical features of dementia with Lewy bodies. The patient died 34 months postimmunization. An autopsy was performed. Main Outcome Measures Neuropathological and biochemical examination of the brain using standardized evaluation for tau, β-amyloid, and synuclein deposits. Results Neither neuropathological nor biochemical examinations showed amyloid deposit in the brain of this immunized patient. For tau deposition, Braak stage was IV/VI, and the Western blot analysis score was 9c/10. The neuropathological semiquantitative score for α-synuclein aggregation was 4. There was no inflammation. These results were compared with those of an age-matched patient with AD and a control devoid of any neurological disease. Conclusion In this Lewy body variant case, with globally stable functional and cognitive features, Aβ immunization resulted in a significant clearance of amyloid deposits, with remaining tau and synuclein pathological features in the brain. Patients with a Lewy body variant of AD should not be excluded from enrollment in Aβ-immunization trials.

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