Table 4.

Overview of tau-targeted immunotherapies in clinical development.

Compound	Type and isotype	Epitope	Targeted tau species	Proposed mechanism	Disease models used
AADvac1	Active, antibody response is mostly IgG1	Primary: 294–305 Secondary: 268–283; 330-335; 362–367	Conformationally altered extracellular tau (monomer, oligomer, fibril), focusing on seeding-capable extracellular tau	Anti-aggregation, opsonisation, inhibition of cell-to-cell spread of neurofibrillary pathology Ref.: (Kontsekova et al., 2014a,Kontsekova et al., 2014b; Novak et al., 2017)	SHR72 rats (tau 151-391/4R), SHR background R3/m4 mice (tau 151-391/34R), C57BL/6 background
ACI-35	Active	pS396 (some sources additionally mention pS404)	Tau pS396 with a conformation that is typically present in the brain of tauopathy patients, preferentially multimeric conformers	Reduction of pS396-tau (soluble and insoluble) Ref.: (Theunis et al., 2013)	P301L tau mice, FVB/Nbackground
ABBV-8E12	Passive, IgG4	25–30	Extracellular tau	Inhibition of cell-to-cell spread of neurofibrillary pathology Ref.: (Yanamandra et al., 2015)	P301S tau mice, B6C3 background
BIIB076	Passive, IgG1	Undisclosed	Monomeric and fibrillary forms, as well as tau isolated from healthy human and Alzheimer’s disease brains.	(undisclosed) Ref: alzforum.org	(Undisclosed)
BIIB092	Passive, IgG4	Exact epitope undisclosed (N-terminal inserts?)	extracellular, N-terminal fragments of tau (eTau)	Secondary reduction of amyloid-β and of neuronal hyperactivity Ref: alzforum.org	JNPL3 P301L mice, C57BL/DBA2/SW background tau-4R/2N-P301L van Leuven mice, C57Bl/6 background
JNJ-63733657	Passive, isotype undisclosed	Undisclosed, presumably mid-region	Seeding-capable tau	Neutralization of tau seeds and reduction of pathology Ref: alzforum.org	(Undisclosed)
LY3303560	Passive, isotype undisclosed	7–9; 313–322	Soluble tau aggregates with intact N-terminus	Neutralization of tau seeds and reduction of pathology. Ref: alzforum.org	(Undisclosed)
RO 7105705	Passive, IgG4	N-terminus	N-terminus of all six isoforms, both monomeric and oligomeric, regardless of phosphorylation status	Inhibition of cell-to-cell spread of neurofibrillary pathology Ref: alzforum.org	(Undisclosed)
UCB0107	Passive, isotype undisclosed	235–246	Seeding-capable extracellular tau	Inhibition of cell-to-cell spread of neurofibrillary pathology Ref: (Courade et al., 2018), alzforum.org	(Undisclosed)

Epitopes numbered according to the 2N4R tau isoform.