Clearance of Amyloid-Beta in Alzheimer's Disease: Shifting the Action Site from Center to Periphery

Yuhui Liu, Yeran Wang, Yang Xiang, Huadong Zhou, Brian Giunta, Noralyn Basco Mañucat-Tan, Jun Tan, X. F. Zhou, Yanjiang Wang

Research output: Contribution to journalReview articlepeer-review

43 Citations (Scopus)

Abstract

Amyloid-beta (Aβ) is suggested to play a causal role in the pathogenesis of Alzheimer’s disease (AD). Immunotherapies are among the most promising Aβ-targeting therapeutic strategies for AD. But, to date, all clinical trials of this modality have not been successful including Aβ vaccination (AN1792), anti-Aβ antibodies (bapineuzumab, solanezumab and ponezumab), and intravenous immunoglobulin (IVIG). We propose that one reason for the failures of these clinical trials may be the adverse effects of targeting the central clearance of amyloid plaques. The potential adverse effects include enhanced neurotoxicity related to Aβ oligomerization from plaques, neuroinflammation related to opsonized Aβ phagocytosis, autoimmunity related to cross-binding of antibodies to amyloid precursor protein (APP) on the neuron membrane, and antibody-mediated vascular and neuroskeletal damage. Overall, the majority of the adverse effects seen in clinical trials were associated with the entry of antibodies into the brain. Finally, we propose that peripheral Aβ clearance would be effective and safe for future Aβ-targeting therapies.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalMOLECULAR NEUROBIOLOGY
Volume51
Issue number1
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Keywords

  • Adverse effects
  • Alzheimer’s disease
  • Amyloid-beta
  • Immunotherapy
  • Peripheral clearance

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