Table 1.

Passive immunotherapy for AD in clinical Phases, adopted from[33], anti-Aβ antibodies in clinical Phases I - III

mAb	Specific for	Clinical trials	References
Bapineuzumab, humanized 3D6	N-terminus (aa 1-5)	Phase III: trials were halted after completion of two trials demonstrated a failure to meet primary outcome measures of cognition and activities of daily living	[41-43]
Solanezumab, humanized m266	central (aa 16-24), accessible only on soluble Aβ	Phase III: ongoing as preventive trial in familial AD (DIAN). Trials failed to meet their primary endpoints in cognition and activities of daily living. A subsequent analysis of mild AD patients pooled from both trials showed a significant effect on cognition.	[44-46]
Gantenerumab, full human mAb	N-terminal (aa 3-12) and C-terminus (aa 18-27)	Phase III: ongoing in prodromal AD patients (DIAN), amyloid reduction but also ARIAs were observed in Phase I.	[47,48]
IVIG containing polyclonal NAbs-Aβ: Gammagard, Octagam, New Gam, Flebogamma	most NAbs-Aβ bind central and C-terminus as well as pathogenic conformations of Aβ (focus on dimers)	Phase III (Gammagard): ongoing, (improved cerebral glucose metabolism and cognitive stabilization of AD symptoms was shown in small clinical studies, too small for statistical evaluation)	[49-51]
		Phase III (Plasmapheresis with infusion of 20% albumin and Flebogamma): ongoing
		Phase II (Octagam): cognition endpoints not met, but improved cerebral glucose metabolism
		Phase II (NewGam): ongoing
Crenezumab, humanized mMABT	conformational epitopes including oligomeric and protofibrillar forms, (aa 13-14 appears relevant)	Phase II: ongoing as long-term safety extension study.	[52]
		Preventive trial in an extended family carrying a presenilin-1 mutation, which causes early onset AD planned for 2013.
BAN2401, humanized mAb158	binds large-size Aβ protofibrils (>100 kDa)	Phase II: ongoing	[53,54]
GSK933776	N-terminus of Aβ	Phase I: two clinical trials for AD are completed and one for macular degeneration is ongoing. Further development for macular degeneration is in Phase II.	[55]
AAB-003, Fc-engineered Bapineuzumab	N-terminal (aa 1-5)	Phase I: ongoing. Lower toxicity (ARIAs) compared to Bapineuzumab is expected. Continuation as open-label extension study	[56]
SAR228810, humanized mAb 13C3	protofibrils, and low molecular weight Aβ	Phase I: ongoing	[57]
BIIB037/BART, full human IgG1	binds insoluble fibrillar human Aβ	Phase I: ongoing in prodromal AD patients	[58,59]

(aa, amino acid; Aβ, Amyloid-β; ApoE4, ApolipoproteinE4; ARIA, amyloid-related imaging abnormalities; DIAN, Dominantly Inherited Alzheimer Network; IVIG, Intravenous Immunoglobulin; NAbs-Aβ, natural occurring polyclonal Anti-Aβ antibodies).