An update on the toxicity of Aβ in Alzheimer’s disease

Abstract

Alzheimer’s disease is characterized histopathologically by deposition of insoluble forms of the peptide Aβ and the protein tau in brain. Aβ is the principal component of amyloid plaques and tau of neurofibrillary tangles. Familial cases of AD are associated with causal mutations in the gene encoding the amyloid precursor protein, APP, from which the amyloidogenic Aβ peptide is derived, and this supports a role for Aβ in disease. Aβ can promote tau pathology and at the same time its toxicity is also tau-dependent. Aβ can adopt different conformations including soluble oligomers and insoluble fibrillar species present in plaques. We discuss which of these conformations exert toxicity, highlight molecular pathways involved and discuss what has been learned by applying functional genomics.

Keywords:

• amyloid
• mitochondria
• oligomer
• proteomic
• tau
• transgenic

Acknowledgments

JG is a Medical Foundation Fellow and has been supported by the University of Sydney, the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the New South Wales Government through the Ministry for Science and Medical Research (BioFirst Program), the Nerve Research Foundation, the Medical Foundation (University of Sydney) and the Judith Jane Mason and Harold Stannett Williams Memorial Foundation.

Disclosures

The authors have no conflicts of interest to disclose.