Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization.

摘要: Background: AD is characterized by cerebral deposition of β-amyloid plaques with amyloid β-peptide (Aβ) 42 as the major peptide constituent, along neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Aβ42 removes these improves cognitive function. A Phase I study in patients demonstrated good safety tolerability multiple injections aggregated (AN1792) QS-21 adjuvant. Methods: Three hundred seventy-two mild to moderate were randomized receive IM AN1792 or placebo (4:1) at baseline months 1, 3, 6, 9, 12 a multicenter II safety, tolerability, pilot efficacy study. Dosing was terminated after four early reports meningoencephalitis, but follow-up continued. The remains blinded, further results will be reported its termination. Results: Symptoms laboratory findings consistent meningoencephalitis occurred 18 298 (6%) treated compared 0 74 on ( p = 0.020). Sixteen had received two doses, one dose, three doses drug before symptoms occurred. median latency from first last 75 40 days. No case later than 6 immunization. Anti-Aβ42 antibody titers not correlated occurrence severity relapses. Twelve recovered close within weeks, whereas six remain disabling neurologic sequelae. All alive date (December 31, 2002), >1 year symptom onset. Conclusions: Postvaccination without clear relation serum anti-Aβ42 titers. Potential mechanisms such T-cell microglial activation may responsible are under consideration develop safer anti-Aβ immunotherapy for AD.