Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies
Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?
Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry
Affiliations: Departments of Neuroscience and Physiology, and Psychiatry, Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA
Correspondence:
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Correspondence to: Einar M. Sigurdsson, PhD, Department of Neuroscience and Physiology, Neuroscience
Institute, New York University Grossman School of Medicine, Science Building, 11th floor, Room SB1115, 435 East
30th Street, New York, NY 10016, USA. Tel.: +1 212 263 3913; E-mail: einar.sigurdsson@nyulangone.org.
Abstract: The tau protein undergoes pathological changes in Alzheimer’s disease and other tauopathies that eventually lead to functional impairments. Over the years, several therapeutic approaches have been examined to slow or halt the progression of tau pathology but have yet to lead to an approved disease-modifying treatment. Of the drugs in clinical trials that directly target tau, immunotherapies are the largest category and mostly consist of antibodies in different stages of development. There is a reasonable optimism that at least some of these compounds will have a clinically meaningful efficacy. This view is based on the significant although modest efficacy of some antibodies targeting amyloid-β in Alzheimer’s disease and the fact that tau pathology correlates much better with the degree of dementia than amyloid-β lesions. In Alzheimer’s disease, clearing pathological tau may therefore improve function later in the disease process than when removing amyloid-β. This review provides a brief update on the active and passive clinical tau immunization trials with insight from preclinical studies. Various epitopes are being targeted and some of the antibodies are said to target extracellular tau but because almost all of pathological tau is found intracellularly, the most efficacious antibodies should be able to enter the cell.
