APOE Antibody - N-terminal region (ARP54283_P050) 

Fragmentation of Apolipoprotein E4 is Required for Differential Expression of Inflammation and Activation Related Genes in Microglia Cells.

In International Journal of Neurodegenerative Disorders on 26 October 2021 by Rohn, T. T., Beck, J. D., et al.

The apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer's disease (AD) and accumulating evidence suggests that fragmentation with a toxic-gain of function may be a key molecular step associated with this risk. Recently, we demonstrated strong immunoreactivity of a 151 amino-terminal fragment of apoE4 (E4-fragment) within the nucleus of microglia in the human AD brain. In vitro, this fragment led to toxicity and activation of inflammatory processes in BV2 microglia cells. Additionally, a transcriptome analysis following exogenous treatment of BV2 microglia cells with this E4 fragment led to a > 2-fold up regulation of 1,608 genes, with many genes playing a role in inflammation and microglia activation. To extend these findings, we here report a similar transcriptome analysis in BV2 microglia cells following treatment with full-length ApoE4 (FL-ApoE4). The results indicated that full-length ApoE4 had a very small effect on gene expression compared to the fragment. Only 48 differentially expressed genes (DEGs) were identified (p < 0.05, and greater than 2-fold change). A gene ontology analysis of these DEGs indicated that they are not involved in inflammatory and activation processes, in contrast to the genes up regulated by the E4-fragment. In addition, genes that showed a negative fold-change upon FL-E4 treatment typically showed a strong positive fold-change upon treatment with the fragment (Pearson's r = -0.7). Taken together, these results support the hypothesis that a key step in the conversion of microglia to an activated phenotype is proteolytic cleavage of FL-ApoE4. Therefore, the neutralization of this amino-terminal fragment of ApoE4, specifically, may serve as an important therapeutic strategy in the treatment of AD.

Evaluation of Apolipoprotein E Fragmentation as a Biomarker for Alzheimer's Disease.

In Journal of Neurology and Neurological Disorders on 1 September 2017 by Gause, J. W., Day, R. J., et al.

Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correlated with AD, ELISA assays were performed with cerebral spinal fluid (CSF) and plasma samples utilizing an antibody that specifically detects a 17 kDa amino-terminal fragment (p17) of APOE (nApoECF antibody). In CSF samples, levels of APOE fragmentation were minimal in both neuropathological normals (NPNs) and AD cases and there were no significant differences between the two cohorts across APOE genotypes. Similar results were found in plasma samples where the p17 APOE fragment comprised only 8.4% of the total level of identified APOE. As with CSF, there were no significant differences found between NPNs and AD cases in terms of the amount of nApoECF quantified. Taken together, these results suggest that the p17 amino-terminal fragment of APOE is not correlated with AD or APOE genotype in the plasma or CSF.

Publications

J W Gause, R J Day, C A Caraway, W W Poon, T T Rohn. Evaluation of Apolipoprotein E Fragmentation as a Biomarker for Alzheimer's Disease.. J Neurol Neurol Disord. 3, (2017). WB 29520379

Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn. Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer's disease brain.. Int J Physiol Pathophysiol Pharmacol. 9, 40-57 (2017). WB 28533891

Tested Species Reactivity:Human, Mouse, Rat

Predicted Species Reactivity:Human

Product Format Liquid. Purified antibody supplied in 1x PBS buffer with 0.09% (w/v) sodium azide and 2% sucrose.

Clonality:Polyclonal

Host:Rabbit

Application:WB, IHC

Additional Information IHC Information: Human Adrenal: Formalin-Fixed, Paraffin-Embedded (FFPE)

IHC Information: Human Kidney: Formalin-Fixed, Paraffin-Embedded (FFPE)

Reconstitution and Storage:For short term use, store at 2-8C up to 1 week. For long term storage, store at -20C in small aliquots to prevent freeze-thaw cycles.

Immunogen:The immunogen is a synthetic peptide directed towards the N terminal region of human APOE

Purification:Affinity Purified

Predicted Homology Based on Immunogen Sequence Human: 100%

Peptide Sequence:Synthetic peptide located within the following region: KVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRF

Concentration:0.5 mg/ml

Blocking Peptide:For anti-APOE (ARP54283_P050) antibody is Catalog # AAP54283 (Previous Catalog # AAPP31032)

Reference:Ho,R.C., (2008) Am J Geriatr Psychiatry 16 (6), 519-522

Gene Symbol:APOE

Gene Full Name:Apolipoprotein E

Alias Symbols:AD2, LPG, APO-E, ApoE4, LDLCQ5

NCBI Gene Id:348

Protein Name:Apolipoprotein E

Description of Target:Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants.Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and APOC2. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Entrez Gene record to access additional publications.

Uniprot ID:P02649

Protein Accession #:NP_000032

Nucleotide Accession:#NM_000041

Protein Size (# AA):317

Molecular Weight:36 kDa

Protein Interactions:LCAT; ARFGAP1; ALB; C19orf52; LOXL4; PRAM1; MID1IP1; ANKH; FBXL12; FXYD7; ECSIT; PDCD4; IFIT5; MAST1; EPN2; PLEKHA6; CDC37; IQSEC1; LONP1; TYRO3; PRDX2; ST13; RPL4; RHEB; PSEN1; HTRA1; PCMT1; ZNF558; NOS3; IFIT3; GCDH; FOXG1; FARSA; ELAVL1; CYP2C18; CYP2C

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