APP

Amyloid Precursor Protein (APP), b-Amyloids (b1-40, 1-42)
& Endoplasmic Reticulum Associated Binding Protein (ERAB) Antibodies

Items	Peptide Antigen location	Ab Host	Neat Antiserum 100 ul Cat #	Affinity Pure Ab Or Mab 100 ug Cat #	Control Peptide 100 ug Cat #
ERAB (Ab # 1)	H, 17 aa, I	Rb, poly	ERAB11-S	ERAB11-A	ERAB11-P
ERAB (Ab # 2)	H, 15 aa, I	Rb, poly	ERAB12-S	ERAB12-A	ERAB12-P
APP770 (Ab #1)	H, 15 aa, I	Ch, poly	APP11-S	-	APP11-P
APP (Ab # 2)	H, 20 aa, NT	G, poly	APP12-S	.	APP12-P
APP (Ab # 3)	H, 21 aa, NT	M, mono		APP13-M
APP (Ab # 4)	H, 16 aa ~CT	G, poly	APP14-S	.	APP14-P
b-amyloid (1-40) Specific for 1-40	H 1-40, ~CT	Rb, poly	BAM401-S	BAM401-A	BAM401-P
b-amyloid (1-40/42)	H, beta 1-40 (~CT)	Rb, poly	BAM402-S	-	BAM402-P
b-amyloid (1-40/42)	H, 1-40 ~NT (1-13aa)	M, mono		BAMP403-M
b-amyloid (1-40/42)	H, 1-40 (10-24 aa)	G, poly	BAM404-S		BAM404-P
b-amyloid (1-42) Specific for 1-42	H, 1-42, ~CT	Rb, poly	BAM421-S	BAM421-A	BAM421-P

Full length Human b-amyloids (1-40), b1-42, $195 per mg; Discounts available for bulk purchases. H=human, M=Mouse, R=Rat, B=Bovine, G=Goat, Rb=Rabbit; NT/CT=Near N or C-terminus; I=Internal sequence.

Amyloid Precursor Protein (APP), b-Amyloids (b1-40, 1-42) & Endoplasmic Reticulum Associated Binding Protein (ERAB)-General Information

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognition in the elderly. A number of genes have been linked in the initiation and development of AD. One of the most important and initial step involves proteolytic cleavage of amyloid precursor protein (APP, chromosome 21) releasing short 40, 42 & 43 aa peptides (beta amyloid1-40, 1-42, and 1-43). Polymerization of beta-amyloid (Ab) and subsequent neuronal deposit (amyloid) leads to the degeneration of neurons involved in memory and cognition. Mutations in the APP gene cause some forms of familial AD (FAD) by releasing an increased amounts of b-amyloid. The AD Ab deposits also contain anti-chymotrypsin (ACT), and Apolipoprotein (Apo-E) that may promote Ab polymerization. Although, Ab deposits or plaques are central to neuropathogenesis and neurodegeneration, it is not clear how it affect neuronal functions. An early onset of FAD has been linked to some 30 mutations in two related genes, Presenilins-1 (PS-1 on chromosome 14; 467 aa) and Presenilins-2 (PS-2 on chromosome 1; 448 aa). PS-1/2 has been co-localized in subcellular sites involved in cell cycle regulation and mitosis (the nuclear membrane, interphase kinetochore, etc).

Most recently, an intracellular protein termed ERAB (262 aa, Endoplasmic reticulum associated binding protein on chromosome X) has been cloned and linked with Ab neurotoxicity. ERAB has structural homology with short-chain alcohol dehydrogenases (hydroxysteroid dehydrogenases and acetyl-CoA reductases). Interestingly, ERAB localizes to endoplasmic reticulum despite the absence of a classical transmembrane sequence. However, in the presence of Ab, ERAB- Ab complex translates to the inner plasma membrane. Alzheimer patients have strong ERAB activity. Normal brains have virtually no ERAB. In addition, Ab neurotoxicity can be reduced by blocking ERAB.

Ab deposits have also been found to contain 2 additional proteins termed a-Synuclein and b-Synuclein. The 140 aa a-Synuclein is identical with non- Ab component (NACP) of AD. The 134 aa b-Synuclein is homologous to 14 kDa bovine phosphoneuroprotein 14. Parkinson's Disease, another form of neurodegenerative disorder that is characterized by tremors and irregular halting movements, has been linked with defects in a-Synuclein gene have in a large Italian family. A mutation in a-Synuclein gene causing a replacement of alanine with a threonine has the potential to cause the protein to misfold.

Using specific peptides, ADI has produced antibodies to various proteins that have been linked with AD. The appropriate control immunogenic peptides are also available to confirm specificity of antibodies.