An update on the toxicity of Abeta in Alzheimer's disease.
Alzheimer's disease is characterized histopathologically by deposition of insoluble forms of the peptide Abeta and the protein tau in brain. Abeta 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 Abeta peptide is derived, and this supports a role for Abeta in disease. Abeta can promote tau pathology and at the same time its toxicity is also tau-dependent. Abeta 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.
Götz
Jürgen
J
Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett St, Camperdown, NSW 2050, Australia. jgoetz@med.usyd.edu.au
Ittner
Lars M
LM
Schonrock
Nicole
N
Cappai
Roberto
R