P3‐427: Passive tau immunotherapy diminishes functional decline and clears tau aggregates in a mouse model of tauopathy

Tau immunotherapy for Alzheimer's disease

“…The efficacy of the vaccine was confirmed in a different mouse model (hTau/PS1) not driven by mutant tau [67]. Around the same time and subsequently, similar effects were obtained with the PHF1 antibody, which recognizes the pS396/pS404 epitope, as well as other antibodies against this epitope developed in the Sigurdsson laboratory at New York University (NYU) School of Medicine [43,44,68,69].…”

“…These were developed originally as diagnostic tools that could differentiate between pathological and normal tau in AD and control brain material. Evaluation of the therapeutic utility of the PHF1 and MC1 antibodies was demonstrated in P301S and JNPL3 (P301L) mice [43,44,58,59]. PHF1 recognizes a linear phospho-tau epitope (pS396, pS404) whereas MC1 is a conformation-dependent antibody that recognizes a structural tau epitope requiring two distinct parts of the linear sequence, an epitope within residues 46-202 and a C-terminal epitope between residues 312 and 342 [60,61].…”

Recent Developments in Tau-Based Therapeutics for Neurodegenerative Diseases

“…More recently, the passive immunotherapy has been tested in vivo by injecting anti-phospho-tau antibody PHF1 intraperitoneally to JNPL3 tau transgenic mice. Preliminary data indicated that treated animals showed decrease tau pathology and functional impairments in these models [97]. Feasibility of this approach will require further studies in different animal models to confirm the reported preliminary findings.…”

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

“…We subsequently showed that this immunogen worked as well in a different tauopathy mouse model, htau/PS1, that does not have a tau mutation, and in which cognitive improvements were detected following the immunization regimen [4]. In later studies, we showed that tau antibodies could have the same effect [5,6], and provided various insights into the possible mechanisms of clearance [7–19]. These studies have been confirmed and extended by various groups showing benefits of immune-targeting the pS396/404 tau epitope [2,4,6–9,12,20–27], and other tau epitopes [20,23–25,27–49], which as mentioned above has resulted in eight clinical trials (for a recent review of these trials see [50]), with several more likely to be initiated in the near future.…”