EK-ELK3424 - mouse-saa2serum-amyloid-a2-elisa-kit

For cellular and molecular biology applications

Amyloid β-peptide (1-40) showed both neurotrophic and neurotoxic effects in dependence on the neuronal age and the concentration of the β-protein. Aβ 1-40 has been used as well as Aβ 1-42 to detect amyloid β-protein multimers in the cerebrospinal fluid of Alzheimer’s disease patients. The sequence of this peptide corresponds to the sequence of human, bovine, canine, feline, ovine, guinea pig, and rabbit Aβ40. The inverted sequence can be used as inactive control in experiments employing Aβ 1-40. For detailed descriptions of the preparation of wild-type and mutant Aβ 1-40 monomers and protofibrils please see the paper of Jan, Hartley, and Lashuel.

Aβ 1-42, 42-residue fragment of amyloid precursor protein, has been found to be a major constituent of the senile plaques formed in the brains of patients with Alzheimer’s disease and late Down’s syndrome. Aβ 1-42 readily forms neurotoxic oligomers at physiological pH. On the other hand, the peptide shows antimicrobial activity. The sequence of this peptide corresponds to the sequence of human, bovine, canine, feline, ovine, guinea pig, and rabbit Aβ42. The peptide has been used to detect amyloid β-protein multimers in the cerebrospinal fluid of Alzheimer’s disease patients through fluorescence correlation spectroscopy. For detailed descriptions of the preparation of Aβ 1-42 monomers and protofibrils please see the papers of Jan, Hartley, and Lashuel, Stine et al. (2011), and of Broersen and colleagues. The findings of Ryan et al. indicate that 10% ammonia disaggregates Aβ42 more efficiently than HFIP.

Injection of the amyloid β-protein fragment VHHQKLVFFAEDVGSNK into different limbic system structures in mice impaired retention with remarkably similar efficacy and in a dose-dependent manner. Aβ (12-28) and other Aβ fragments may exert dysregulatory cognitive effects by incoordination of K⁺ channel function in neurons, glia and endothelial cells.

The amyloid β-protein is a 39- to 43-amino acid polypeptide that is the primary constituent of senile plaques and cerebrovascular deposits in Alzheimer’s disease and Down’s syndrome. Additionally it acts as an inhibitor of the ubiquitin-dependent protein degradation in vitro.

The remarkable histochemical features of Alzheimer’s disease (AD) are plaques that contain cores of extracellular filaments, which have been identified as amyloid substance. The major component of this amyloid is the β-protein. The synthetic peptide, having the same sequence as the N-terminal 28 residues, formed fibrils that have the same antigenic and structural features like the native AD amyloid filaments.

Reverse sequence of Aβ 1-42, inactive control for the Aβ.

The reverse sequence of Aβ 25-35 is used as inactive control.

Reverse sequence of Aβ 1-40. Inactive control for Aβ40.

Like Aβ (25-35), the Aβ fragment (1-38) destabilizes calcium homeostasis and renders human cortical neurones vulnerable to environmental insults.

The biologically active domain of the amyloid β-protein for neurotrophic and neurotoxic effects is located in the β (25-35) sequence GSNKGAIIGLM, which is homologous to a region in peptides of the tachykinin family.

The Cu²⁺ complex of this soluble amyloid β-protein fragment showed significant oxidative activities toward the catechol-like substrate 1,2,3-trihydroxylbenzene (pyrogallol) and plasmid DNA cleavage. The N-terminal Aβ fragments Aβ1-14, Aβ1-15, and Aβ1-16 are elevated in cell media and in CSF in response to γ-secretase inhibitor treatment. The fragments can serve as biomarkers in clinical studies of the effect of such inhibitors.

The amyloid precursor protein (APP) is cleaved within the amyloid β-protein region by a putative APP secretase to release its extracellular portion. Gelatinase A, the matrix metalloproteinase MMP-2, possesses such APP secretase-like activity, effectively hydrolyzing also the synthetic amyloid β-protein fragment (10-20) YEVHHQKLVFF at the normal processing site, the Lys¹⁶-Leu¹⁷ bond (Km approx. 0.13 mM).

Cleavage of APP by alpha- and gamma-secretase (i.e. the non-amyloidogenic pathway) yields p3 peptide, a mix of Aβ 17-40 and Aβ 17-42. p3 is a major constituent of diffuse plaques observed in AD brains and pre-amyloid plaques in people affected by Down syndrome.