Amyloid Beta Peptide 1-42 Monomers

Our amyloid beta peptide 1-42 (Aβ42) is produced synthetically and treated with 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) prior to drying which breaks down pre-formed fibrils and monomerizes the peptide, as previously published (1,2) . Upon resuspension in Ammonium hydroxide (NH4OH), our Aβ42 presents as a monomeric peptide without fibrils when observed under TEM, AFM and on a Western Blot with an anti-amyloid beta antibody. In contrast to AB42 oligomer and fibril constructs, our Aβ42 monomers were not toxic to primary rat cortical neurons. In the brain, amyloid beta peptide (Aβ) is generated by protease cleavage of amyloid precursor protein (APP), which aggregates into oligomers, protofibrils, fibrils and ultimately plaques in neurodegenerative diseases. The accumulation of Aβ plaques in the brain is considered a hallmark of Alzheimer’s disease (AD), and most of the drugs tested for AD in the past 20 years have targeted amyloid beta accumulation (3) . Soluble Aβ oligomers isolated from the brains of AD patients or those generated in vitro potently impaired synapse structure and function (4) . Aβ oligomers generated in vitro were toxic to PC12 cells (2) and SH-SY5Y cells (5) . Aβ was demonstrated to interact with tauopathies to affect neurodegeneration in AD patients (6) and accumulations of Aβ were shown to be associated with lower survival rates in Parkinson’s disease patients with dementia (7) .

1. Stine et al. 2003. JBC. 278(13):11612-22. doi: 10.1074/jbc.M210207200 2. Chromy et al. 2003. Biochemistry. 42:12749-12760. doi: 10.1021/bi030029q 3. Panza et al. 2019. Nat Rev Neurol. 15:73-88 https://doi.org/10.1038/s41582-018-0116-6 4. Shankar et al. 2008. Nat Med. 14(8):837-842. doi: 10.1038/nm1782 5. Kayed et al. 2003. Science. 300(5618): 486-489. doi: 10.1126/science.1079469 6. Want et al. 2016. JAMA Neurol. 73(9):1070-7. doi: 10.1001/jamaneurol.2016.2078 7. Kotzbauer et al. 2012. Arch Neurol. 69(10): 1326-1331. doi: 10.1001/archneurol.2012.1608

1. Stine et al. 2003. JBC. 278 (13) :11612-22. doi: 10.1074/jbc.M210207200 2. Chromy et al. 2003. Biochemistry. 42:12749-12760. doi: 10.1021/bi030029q 3. Panza et al. 2019. Nat Rev Neurol. 15:73-88 https://doi.org/10.1038/s41582-018-0116-6 4. Shankar et al. 2008. Nat Med. 14 (8) :837-842. doi: 10.1038/nm1782 5. Kayed et al. 2003. Science. 300 (5618) : 486-489. doi: 10.1126/science.1079469 6. Want et al. 2016. JAMA Neurol. 73 (9) :1070-7. doi: 10.1001/jamaneurol.2016.2078 7. Kotzbauer et al. 2012. Arch Neurol. 69 (10) : 1326-1331. doi: 10.1001/archneurol.2012.1608