Title | Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Sigurdsson, EM |
Journal | J Alzheimers Dis |
Volume | 101 |
Issue | s1 |
Pagination | S129-S140 |
Date Published | 2024 |
ISSN | 1875-8908 |
Keywords | Alzheimer Disease, Animals, Clinical Trials as Topic, Humans, Immunotherapy, tau Proteins, Tauopathies |
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. |
DOI | 10.3233/JAD-231238 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 38427486 |
PubMed Central ID | PMC11587787 |
Grant List | R21 AG069475 / AG / NIA NIH HHS / United States R56 AG083436 / AG / NIA NIH HHS / United States R01 NS077239 / NS / NINDS NIH HHS / United States R21 AG058282 / AG / NIA NIH HHS / United States R01 NS120488 / NS / NINDS NIH HHS / United States RF1 NS120488 / NS / NINDS NIH HHS / United States R01 AG032611 / AG / NIA NIH HHS / United States |