Tau-targeting therapies for Alzheimer disease.
Nat Rev Neurol
; 14(7): 399-415, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29895964
ABSTRACT
Alzheimer disease (AD) is the most common form of dementia. Pathologically, AD is characterized by amyloid plaques and neurofibrillary tangles in the brain, with associated loss of synapses and neurons, resulting in cognitive deficits and eventually dementia. Amyloid-ß (Aß) peptide and tau protein are the primary components of the plaques and tangles, respectively. In the decades since Aß and tau were identified, development of therapies for AD has primarily focused on Aß, but tau has received more attention in recent years, in part because of the failure of various Aß-targeting treatments in clinical trials. In this article, we review the current status of tau-targeting therapies for AD. Initially, potential anti-tau therapies were based mainly on inhibition of kinases or tau aggregation, or on stabilization of microtubules, but most of these approaches have been discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting therapies in clinical trials are immunotherapies, which have shown promise in numerous preclinical studies. Given that tau pathology correlates better with cognitive impairments than do Aß lesions, targeting of tau is expected to be more effective than Aß clearance once the clinical symptoms are evident. With future improvements in diagnostics, these two hallmarks of the disease might be targeted prophylactically.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
/
Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Rev Neurol
Ano de publicação:
2018
Tipo de documento:
Article