Anti-Amyloid Beta 3NTyr10 Antibody, clone 4A5E8 clone 4A5E8, from mouse

Deposition of Amyloid beta (Ab) is an early event in the pathogenesis of Alzheimer s disease (AD). Ab peptides originate from the proteolytic cleavage of the amyloid precursor protein (APP). The beta-secretase cleaves APP between residues Met671 and Asp672 and yields sAPP beta and C99. Following the beta-secretase cleavage, a second cleavage occurs at the C-terminus of Ab peptide that releases Ab from C99. This cleavage occurs in the vicinity of residue 712 of the C-terminus. The gamma-secretase can cleave the C-terminal region at either Val711 or Ile713 to produce the shorter Ab peptide (Ab1-40) or the longer Ab peptide (Ab1-42). Ab1-42 occurs more frequently and forms fibrillar aggregates far more readily than the Ab1-40 peptide. In AD, upregulation of inducible nitric oxide synthase (NOS2), results in tyrosine nitration of several proteins, including Ab, which accelerates its aggregation. APP/PS1/Nlrp3 mice display less nitrated Ab and a reduced average plaque size as well as fewer nitrated plaque cores. NOS2 deficiency and treatment with NOS2 inhibitors is shown to reduce 3NTyr (10)-Ab and overall Ab deposition and cognitive dysfunction in APP/PS1 mice. Also, injection of 3NTyr(10)-A into the brain of young APP/PS1 mice leads to induction of beta-amyloidosis. (Ref.: Heneka, MT et al (2013). Nature 493, 674-678; Kummer, MP et al (2011). Neuron. 71(5):833-844).