Alzheimer's Disease Related Products - b-Amyloid
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Deposition of Ab is an early event in the pathogenesis of AD that precedes the formation of Tau-positive paired helical filaments (PHFs) in NFTs. AD is also characterized by a progressive deposition of the Ab peptides in senile plaques. In normal healthy individuals, Ab peptides are present only in small quantities as soluble monomers that circulate in cerebrospinal fluid and blood. However, in AD patients, their levels are significantly increased and they begin to accumulate as insoluble, fibrillar plaques. The Ab core in senile plaques varies in length from 38 to 43 amino acids, however, Ab42 occurs more frequently and forms fibrillar aggregates far more readily than the Ab40 peptide. Ab peptides originate from the proteolytic cleavage of the amyloid precursor protein (APP). The b-amyloid gene, located on chromosome 21, encodes a transmembrane amyloid precursor protein (APP). APP is reported to occur in three common isoforms, APP695, APP751, and APP770. The APP695 is expressed exclusively in neurons, whereas APP751 and APP770 are present in both neural and non-neural cells. The primary structure of APP contains a small signal sequence, a large extramembranous N-terminal region, a single transmembrane domain, and cytoplasmic C-terminal tail.
Neuronal toxicity to Ab occurs via several different mechanisms of which free radical induced damage appears to be the most prominent one. Ab can activate inflammatory pathways by enhancing the microglial secretion of inflammatory cytokines, such as IL-1 and IL-6. Additionally, it can trigger the production of ROS, nitrogen intermediates, and TNF-a from microglia. Ab also increases the accumulation of H2O2 in a Cu2+/Zn2+-dependent manner, which can lead to free radical-induced lipid peroxidation and cell death. In vitro, Ab42 is shown to induce apoptosis in cultured cortical neurons, possibly through alterations of cellular calcium homeostasis. Interaction between Ab and ApoE3 or E4 is considered to be an important determinant of amyloidosis. ApoE3 is shown to inhibit Ab aggregation in vitro by decreasing Ab multimers, whereas ApoE4 is reported to accelerate the rate of amyloid fibril formation (Ab42 > Ab40).
Antibodies to b-Amyloids, Amyloid Precursor Proteins & Related Products
Amyloid Related Proteins and Peptides
Amyloid Probes and Stains
Amyloidogenesis Inhibitors and Related Products
