Alzheimer's Disease Antibodies
GenScript offers a wide selection of antibodies relevant to the biochemical pathways affected in the course of Alzheimer's, including APP, Tau protein, β-Amyloisd, Ubiquitin, β-Secretase, γ-Secretase, GSK3, and many other hot targets.
APP protein is highly conserved among species. APP gene generates three predominant transcripts: APP695 (exons 1-6, 9-18, excluding 13a), APP751 (exons 1-7, 9-18, excluding 13a), and APP770 (exons 1-18, excluding 13a). Both APP751 and APP770 contain exon 7, which encodes a serine protease inhibitor (Kunitz protease inhibitor) domain. APP695 is a predominant variant in neurons. APP751 is more common in other tissues. The beta-amyloid protein is encoded by exons 16 and 17. GenScript offers a set of antibodies to different regions of APP combinations of which can be used to distinguish between different isoforms of APP in Western blot and immunohistochemistry.
Abeta-based etiology of AD is supported by the identification of missense mutations associated with familial, early-onset AD. These mutations are found in and around the Abeta region of APP, and affect APP processing by several A-beta-generating proteases, including alpha (ADAM17), beta (BACE) and gamma secretases. Gamma-secretase is a protein complex, which incorporates presenilin (PS1), nicastrin, APH1, and PEN2 proteins. Presenilins are also targets of many AD-associated mutations. Once generated, Abeta can be degraded by other proteases including insulin degrading enzyme (IDE) and neprilysin (CD10). GenScript offers a set of antibodies to different APP cleavage products and APP-processing and clearance enzymes.
The phosphorylation status of amyloid precursor protein (APP) at Thr668 plays a role in the proteolytic cleavage of APP, which could generates either soluble APP(beta) (sAPP(beta)/APPs beta) and Abeta, or soluble APP(alpha) (sAPP(alpha)/ alpha APPS) and a C-terminal fragment of Abeta. The proteolytic processing that generates the amyloid ?-peptide (A?) also releases into the cytoplasm the carboxy-terminal fragment of APP, gamma-CTF, known to translocate int the nucleus and initiate transcription of certain target genes enhanced by FE65/APBB1. Phosphorylation of APP at Thr668 is involved in neurite extension and anterograde vesicular transport. By contrast, increased phosphorylation of APP on this residue is a pathological trait of Alzheimer's disease. Normal APP phosphorylation is linked to c-Jun NH2-terminal kinase modulated by glycogen synthase kinase 3. Phosphorylation of APP in degenerating neurons is linked to the activation of cyclin-dependent kinase 5 (cdk5). Phosphorylation of APP at Tyr757 and 762 is important for MAPK8IP1, APBA1, shcA/shcC, and DAB1 binding. Binding interactions regulated by phosphorylation determine the localization and the function of APP. GenScript offers antibodies to these phosphorylated forms of APP.
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.
|Tau Antibody (Phospho-Ser199), pAb, Rabbit - 40 ug||