Affiliations: Departments of Physiology and Neuroscience, and Psychiatry, New York University School of Medicine, New York, NY, USA
Correspondence:
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Address for correspondence: Einar M. Sigurdsson, Ph.D., Departments of Physiology and Neuroscience, and Psychiatry, New York University School of Medicine, Millhauser Labs. Room HN418, 560 First Avenue, New York, NY 10016, USA. Tel.: +1 212 263 3913; Fax: +1 212 263 6751; E-mail: einar.sigurdsson@med.nyu.edu.
Abstract: Immunotherapies that target the amyloid-β (Aβ) peptide in Alzheimer's disease (AD) have shown promise in animal and human studies. Although the first clinical trial was halted because of adverse reactions, this approach has been refined and additional trials are underway. Another important target in AD is the neurofibrillary tangles, composed primarily of hyperphosphorylated tau proteins, which correlate well with the degree of dementia. As Aβ and tau pathologies are likely synergistic, targeting both should be more effective and may be essential as early diagnosis prior to cognitive decline is currently not available. Also, Aβ immunotherapy only results in a very limited indirect clearance of tau aggregates in dystrophic neurites, showing the importance of developing a separate therapy that directly targets pathological tau. Our findings in two tangle mouse models indicate that immunization with a phospho-tau derivative reduces aggregated tau in the brain and slows progression of the tangle-related behavioral phenotype. These antibodies enter the brain and bind to pathological tau within neurons. We are currently clarifying further the mechanism of action of this promising therapeutic approach and determining its epitope specificity.
