Amyloid beta A4 protein (UniProt P05067; also known as ABPP, Alzheimer disease amyloid protein, Amyloid precursor protein, APP, APPI, Cerebral vascular amyloid peptide, CVAP, PN-II, PreA4, Protease nexin-II) is encoded by the APP (also known as A4, AD1) gene (Gene ID 351) in human. Amyloid precursor protein (APP) is initially produced with a signal peptide sequence (a.a. 1-17), the removal of which yields the mature protein with a large extracellular portion (a.a. 18-699), followed by a transmembrane segment (a.a. 700-723) and a cytoplasmic (a.a. 724-770) tail. APP can be further processed by the alpha-, beta-, and gamma-secretases in two alternative processing pathways. In the non-amyloidogenic pathway, APP is first cleaved by the plasma membrane-localized alpha-secretase to generate an N-terminal extracellular sAPPalpha fragment (a.a. 18-687) and a membrane-bound C-terminal fragment C83 (CTFalpha), which can be further cleaved by gamma-secretase to produce a non-toxic small peptide p3 and a cytoplasmic APP intracellular domain (AICD). In the amyloidogenic pathway, APP undergoes beta-cleavage in BACE-1 (beta-site APP-cleaving enzyme)-enriched endosomes to generate an N-terminal extracellular sAPPbeta fragment (a.a. 18-671) and a membrane-bound C-terminal fragment C99 (CTFbeta). Subsequent cleavage of C99 by gamma-secretase releases the amyloid beta peptides, Abeta1-42 (672-713) & Abeta1-40 (672-711), and AICD. Abeta accumulation in the cortical and hippocampal regions of the brain is a major pathological feature of Alzheimer's disease (AD). Abeta Ser8 phosphorylation is shown to promote Abeta aggregation into oligomeric and fibrillar assemblies and to prevent Abeta proteolytic clearance by certain proteases.
Synonyms: Abeta peptide, Ser8 phosphorylated, Abeta peptide, Ser8 phosphorylated, Amyloid beta peptide, Ser8 phosphorylated, Abeta1-40, Ser8 phosphorylated, Abeta1-42, Ser8 phosphorylated, Abeta1-40, Ser8 phosphorylated, Abeta1-42, Ser8 phosphorylated
Application: Western Blotting Analysis: 2 µg/mL from a representative lot detected 2.5-100 ng of Ser8-phosphorylated synthetic Abeta1-40 peptide, but not non-phosphorylated Abeta1-40 peptide (Courtesy of Dr. Kumar and Prof. Dr. Walter, Department of Neurology, University Bonn, Germany).Western Blotting Analysis: 2 µg/mL from a representative lot detected phosphorylated oligomeric amyloid beta (pAbeta) peptides in 50 µg of brain extract from an 8-month old APP/PS1KI transgenic mouse, but not in extract from an age-matched non-transgenic mouse (Courtesy of Dr. Kumar and Prof. Dr. Walter, Department of Neurology, University Bonn, Germany).ELISA Analysis: Clone 1E4E11 hybridoma culture supernatant detected the immunogen peptide with phosphorylated Ser8, but not the corresponding non-phosphorylated peptide (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709).Immunohistochemistry Analysis: A representative lot detected age-dependent phospho-amyloid beta (pAbeta) immunoreactivity and localization in paraffin-embedded APP/PS1KI mouse brain sections following antigen retrieval by heat and 88% formic acid treatments (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709).Immunofluorescence Analysis: A representative lot detected phospho-amyloid beta (pAbeta) immunoreactivity in cortical neurons colocalized with that detected with a non-phospho-specific Abeta antibody by dual fluorescent immunohistochemistry staining of paraffin-embedded 2-month old APP/PS1KI mice cotex sections following anigen retrieval by heat and 88% formic acid treatments (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709).Western Blotting Analysis: A representative lot detected monomeric, dimeric, trimeric, and oligomeric forms of synthetic Abeta1-40 and Abeta1-42 peptides with phosphorylated Ser8, but not the non-phosphorylated Abeta1-40 and Abeta1-42 peptides (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709).Western Blotting Analysis: A representative lot detected monomeric, dimeric, and oligomeric forms of phosphorylated amyloid beta (pAbeta) peptides in brain extracts from 6- and 12-month old APP/PS1KI transgenic mice, but not in brain extracts from age-matched non-transgenic mice (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709).Note: Formic acid (88%) treatment following heat retrieval is recommended for immunohistochemical detection of aggregated intraneuronal Abeta peptides in brain sections (Kumar, S., et al. (2013). Acta Neuropathol. 125(5):699-709; Christensen, D.Z., et al. (2009). Brain Res. 1301:116-125).
Other Notes: Concentration: Please refer to lot specific datasheet.