%0 Journal Article
%T Intraneuronal A¦Â detection in 5xFAD mice by a new A¦Â-specific antibody
%A Katherine L Youmans
%A Leon M Tai
%A Takahisa Kanekiyo
%A W Blaine Stine
%A Sara-Claude Michon
%A Evelyn Nwabuisi-Heath
%A Arlene M Manelli
%A Yifan Fu
%A Sean Riordan
%A William A Eimer
%A Lester Binder
%A Guojun Bu
%A Chunjiang Yu
%A Dean M Hartley
%A Mary Jo LaDu
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-8
%X MOAB-2 (mouse IgG2b) is a pan-specific, high-titer antibody to A¦Â residues 1-4 as demonstrated by biochemical and immunohistochemical analyses (IHC), particularly compared to 6E10 (a commonly used commercial antibody to A¦Â residues 3-8). MOAB-2 did not detect APP or APP-CTFs in cell culture media/lysates (HEK-APPSwe or HEK-APPSwe/BACE1) or in brain homogenates from transgenic mice expressing 5 familial AD (FAD) mutation (5xFAD mice). Using IHC on 5xFAD brain tissue, MOAB-2 immunoreactivity co-localized with C-terminal antibodies specific for A¦Â40 and A¦Â42. MOAB-2 did not co-localize with either N- or C-terminal antibodies to APP. In addition, no MOAB-2-immunreactivity was observed in the brains of 5xFAD/BACE-/- mice, although significant amounts of APP were detected by N- and C-terminal antibodies to APP, as well as by 6E10. In both 5xFAD and 3xTg mouse brain tissue, MOAB-2 co-localized with cathepsin-D, a marker for acidic organelles, further evidence for intraneuronal A¦Â, distinct from A¦Â associated with the cell membrane. MOAB-2 demonstrated strong intraneuronal and extra-cellular immunoreactivity in 5xFAD and 3xTg mouse brain tissues.Both intraneuronal A¦Â accumulation and extracellular A¦Â deposition was demonstrated in 5xFAD mice and 3xTg mice with MOAB-2, an antibody that will help differentiate intracellular A¦Â from APP. However, further investigation is required to determine whether a molecular mechanism links the presence of intraneuronal A¦Â with neurotoxicity. As well, understanding the relevance of these observations to human AD patients is critical.The form(s) of amyloid-¦Â peptide (A¦Â), particularly the 42 amino acid form (A¦Â42), associated with the neurotoxicity characteristic of Alzheimer's disease (AD) remains unclear. The potential toxic assemblies of the peptide include soluble A¦Â [1], oligomeric A¦Â [2], intraneuronal A¦Â [3] and specific plaque morphology [4]. Evidence indicates that intraneuronal A¦Â accumulation may be an important proximal neurotox
%K Intraneuronal
%K A¦Â
%K APP
%K MOAB-2
%K 3xTg
%K 5xFAD
%K Antibody
%K Alzheimer's disease
%U http://www.molecularneurodegeneration.com/content/7/1/8