Table 2.

α-Synuclein passive immunization studies to date

Animal model	Antigen/antibody	Outcome	Reference
Transgenic mice expressing human α-syn under the PDGF-β promoter, D-line	α-syn C-terminus antibody 9E4 (IgG1), epitope 118-126	Reduction of calpain-cleaved α-syn in neurons. No difference in microglia activation between control and antibody-treated mice. Less motor (rotarod) and cognitive impairment (Morris water maze).	[73]
Transgenic mice expressing human α-syn under the PDGF-β promoter, M-line	α-syn C-terminus antibody 274 (IgG2a), epitope 120-140	Reduced accumulation of α-syn in neurons and astroglia. Increased presence of α-syn in microglia. Improved function in open field and pole tests.	[16]
Transgenic mice expressing human α-syn under the Thy-1 promoter, line 61	C-Terminus α-syn antibodies: 1H7, 9E4, 5C1, and 5D12	Attenuated synaptic and axonal pathology in cortex, hippocampus and striatum. Reduced accumulation of C-terminus-truncated α-syn in striatal axons and mitigated loss of tyrosine hydroxylase fibers. Reduced astrogliosis and microgliosis. Improved motor (round beam test) and memory deficits (Morris water maze).	[85]
Transgenic mice expressing human A30P α-syn under the Thy-1 promoter	α-syn protofibril-selective monoclonal antibody (mAb47)	Reductions of soluble and membrane-associated α-syn protofibrils in spinal cord. No increase in astrocytic or microglial activation.	[80]
Mice overexpressing human α-syn under the PDGF-β promoter (line D)	Single-chain fragment variables against oligomeric α-syn fused to the low-density lipoprotein receptor-binding domain of apolipoprotein B	Decreased α-syn accumulation in neocortex and hippocampus. Oligomeric and phosphorylated α-syn was reduced. Increased neuron numbers and synapses, as well as reduced levels of astrocytes. Improved memory function (Morris water maze).	[82]
Intrastriatal stereotaxic injections of α-syn preformed fibrils in wild type C57Bl6/C3H-mice	Monoclonal antibody: Syn303 (binds pathological conformations of human and mouse α-syn) targeting N-terminus)	Reduction of Lewy-like pathology, amelioration of nigral dopamine neuron loss. No differences in astrogliosis and microgliosis. Improved motor behavior (rotarod, wire hang test and open field activity).	[84]
Fisher 344 male rats injected into substantia nigra with recombinant adeno-associated viral vector expressing human wild type α-syn	Antibodies against the N-terminal or central region of α-syn	Lowered levels of α-syn, reduced α-syn-induced dopaminergic cell loss. Decreased number of activated microglia. Partial improvement of behavioral deficits (cylinder test).	[77]