Alzheimer's Disease Antibodies
GenScript offers a wide selection of antibodies relevant to the biochemical pathways affected in the course of Alzheimer's, including Tau protein, β-Amyloisd, Ubiquitin, γ-Secretase, and many other hot targets.
Besides amyloid plaques, AD is also characterized by the disruption of neuronal cytoskeleton and its replacement by the neurofibrillary tangles composed of paired helical filaments (PHFs). The PHFs are also found in the lesions of other central nervous system disorders. The major molecular constituents of PHFs are bundles of hyperphosphorylated tau and neurofilament (NF) proteins.
Tau, a highly asymmetric and heat-stable protein, is expressed mainly in the brain, where it regulates the stability and orientation of microtubules in neurons, astrocytes, and oligodendrocytes. Tau is highly enriched in the axon where it is involved in anterograde transport. The major function of Tau is to stabilize microtubules and to bundle microtubules in the axon. Phosphorylation reduces the ability of Tau to promote microtubule self-assembly. Tau protein is reported to be the predominant component of the paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) which are characteristic of pathological brain lesions in Alzheimer's disease.
Tau gene produces a family of six isoforms ranging from 352 to 441 amino acids in length. The tau variants differ from each other with the presence of three or four repeat regions close to the carboxy-terminus andone or two inserts near the amino-terminal.
Tau protein, especially in Alzheimer's brains, is phosphorylated at many different sites. At least thirty phosphorylation sites have been described, including Thr39, Ser46, Thr50, Thr69, Thr153, Thr175, Thr181, Ser198, Ser199, Ser202, Thr205, Ser208, Ser210, Thr212, Ser214, Thr217, Thr231, Ser235, Ser237, Ser241, Ser262, Ser285, Ser305, Ser324, Ser352, Ser356, Ser396, Ser400, Thr403, Ser404, Ser409, Ser412, Ser413, Ser416 and Ser422. The hyperphosphorylation of Tau can be achieved by several kinases, including ERK/EPHB2, GSK-3beta, and Tau protein kinase II (TPKII/CDK5). Specifically, TPKII phosphorylates serines 202 and 404. Transfected GSK-3β phosphorylates serines 199, 202, 235, 396, 404 and 413, and threonines 205 and 231. These sites are among the major abnormal phosphorylation sites of tau. GenScript offers antibodies pan/phosphor-specific antibody pairs to the phosphorylation sites shown in bold, please click them to see product information.
Alzheimer's disease (AD) is marked by a gradual deposition of the 4kDa β-amyloid peptide (Aβ) in senile plaques and accumulation of Tau protein as neurofibrillary tangles in the brain. Aβ originate from the proteolytic cleavages of the transmembrane amyloid precursor protein (APP) Amyloidogenic pathway involves the cleavage of APP by β-secretase at the N-terminus and cleavage of APP by γ-secretase at the C-terminus. The misfolded fibrillary form of Aβ (predominantly Aβ42) is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Mutations in both APP and presenilin are associated with early onset of Alzheimer's disease as a result of increased production of Aβ42.
The β-Secretase has also been identified as an aspartyl protease (BACE or Asp-2) e. It has a C-terminal transmembrane domain and two active site motifs located in the luminal domain. The β-secretase cleaves APP between residues Met671 and Asp672 and yields sAPPs and the C99 fragment.
The γ-Secretase is a multi-subunit internal membrane protease that cleaves single pass transmembrane proteins within the transmembrane domain. It consists minimum of 4 proteins: presenilin, nicastrin, APH-1 and PEN-2. Presenilin is an aspartic protease acting as the catalytic subunit of the complex.
The α-secretase (TACE) also acts on APP by its cleavage within the Aβ domain between Lys687 and Leu688.This produces a large soluble α-APP domain and the C-terminal fragment containing P3 and C83. The latter can then be cleaved by γ-secretase at residue 711 or 713 generating P3 fragment. Because this pathway does not yield Aβ peptide diverting APP towards the α-secretase pathway may have a beneficial effect in lowering Aβ peptide levels. α-secretase shares many of its properties with the secretase that cleaves angiotensin-converting enzyme and is believed to be a zinc metalloproteinase of the ADAMs family. Its activity is reported to be enhanced by Muscarinic agonists (M1 and M3) and some PKC activators with considerations for AD treatment.