title: Do anti-amyloid beta protein antibody cross reactivities confound Alzheimer disease research?
abstract: BACKGROUND
  Alzheimer disease (AD) research has focussed mainly on the amyloid beta protein (Aβ). However, many Aβ-and P3-type peptides derived from the amyloid precursor protein (APP) and peptides thought to derive from Aβ catabolism share sequence homology. Additionally, conformations can change dependent on aggregation state and solubility leading to significant uncertainty relating to interpretations of immunoreactivity with antibodies raised against Aβ. We review evidence relating to the reactivities of commonly used antibodies including 6F3D, 6E10 and 4G8 and evaluate their reactivity profiles with respect to AD diagnosis and research.
  
  
  RESULTS
  Antibody cross-reactivities between Aβ-type, P3-type and Aβ-catabolic peptides confound interpretations of immunoreactivity. More than one antibody is required to adequately characterise Aβ. The relationships between anti-Aβ immunoreactivity, neuropathology and proposed APP cleavages are unclear.
  
  
  CONCLUSIONS
  We find that the concept of Aβ lacks clarity as a specific entity. Anti-Aβ antibody cross-reactivities lead to significant uncertainty in our understanding of the APP proteolytic system and its role in AD with profound implications for current research and therapeutic strategies.
authors.affiliation: Department of Public Health and Primary Care, Institute of Public Health Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK. seh66@medschl.cam.ac.uk.
authors.forename: Sally
authors.identifier: http://orcid.org/0000-0002-8063-6556
authors.initials: S
authors.lastname: Hunter
authors.affiliation: Department of Public Health and Primary Care, Institute of Public Health Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D035843:Biomedical Research; D015986:Confounding Factors, Epidemiologic; D003429:Cross Reactions / Q000276:immunology*; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies
keywords: Alzheimer disease; Amyloid beta protein; Amyloid precursor protein; Antibody; Cross reactivity; Experimental design