Late-Onset Alzheimer's Disease Risk Gene Antibody Sampler Kit #36833

Kit Usage Information

Protocols

• 5030: Western Blotting, Immunoprecipitation (Magnetic), Immunofluorescence
• 7074: Western Blotting
• 13366: Western Blotting, Immunoprecipitation (Agarose), Immunohistochemistry (Paraffin), Immunofluorescence
• 34642: Western Blotting, Immunohistochemistry (Paraffin)
• 39327: Western Blotting, Immunohistochemistry (Paraffin)
• 51844: Western Blotting, Immunoprecipitation (Agarose)
• 68258: Western Blotting, Immunoprecipitation (Magnetic), Immunohistochemistry (LEICA® BOND™), Immunohistochemistry (Paraffin), Flow*
• 79322: Western Blotting, Immunofluorescence
• 90673: Western Blotting
• 91068: Western Blotting, Immunoprecipitation (Agarose), Immunofluorescence

Product Description

The Late-Onset Alzheimer's Disease Risk Gene Antibody Sampler Kit provides an economical means of detecting proteins identified as risk factors for late-onset Alzheimer’s Disease (LOAD) by western blot. This kit includes enough antibodies to perform at least two western blot experiments with each primary antibody.

Specificity / Sensitivity

Each antibody in the Late-Onset Alzheimer's Disease Risk Gene Antibody Sampler Kit detects endogenous levels of its target protein. SORL1 (D8D4G) Rabbit mAb recognizes endogenous levels of total SORL1 protein. TREM2 (D8I4C) Rabbit mAb recognizes endogenous levels of total TREM2 protein. Clusterin (D7N2K) XP^® Rabbit mAb recognizes endogenous levels of total Clusterin protein. EphA1 (D6V7I) Rabbit mAb recognizes endogenous levels of total EphA1 protein. MEF2C (D80C1) XP^® Rabbit mAb detects endogenous levels of total MEF2C protein. BIN1 (E4A1P) Rabbit mAb recognizes endogenous levels of total BIN1 protein. The antibody recognizes multiple BIN1 isoforms. ApoE (pan) (D7I9N) Rabbit mAb recognizes endogenous levels of total ApoE protein. This antibody also recognizes overexpressed ApoE2, ApoE3, and ApoE4 proteins. ApoE4 (E5M4L) Rabbit mAb recognizes endogenous levels of total ApoE4 protein. This antibody does not cross-react with ApoE2 or ApoE3 by western blot and is not expected to cross-react with endogenous ApoE2 or ApoE3 by immunohistochemistry. Non-specific staining was observed in kidney by immunohistochemistry. MHC Class II (LGII-612.14) Mouse mAb exhibits strong reactivity with HLA-DRB and weak reactivity with HLA-DPB in cell lines transfected with constructs expressing Myc/DDK-tagged HLA-DRB and HLA-DPB, respectively. Reactivity is not observed with HLA-DMB, HLA-DOB, or HLA-DQB in cell lines transfected with constructs expressing Myc/DDK-tagged HLA-DMB, HLA-DOB, and HLA-DQB.

Source / Purification

Monoclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val266 of human BIN1 protein, Glu267 of human SORL1 protein, Leu221 of human TREM2 protein, Pro285 of human ApoE protein, Ser396 of human Clusterin protein, Arg130 of human ApoE4 protein, Met182 of human MEF2 protein, and a recombinant protein fragment specific to the extracellular domain of human EphA1 protein. MHC Class II (LGII-612.14) Mouse mAb is produced by immunizing animals with cultured human B lymphoid cells treated with IFN-gamma.

Background

Alzheimer's Disease (AD) is the leading cause of dementia worldwide. Clinically, it is characterized by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles, which result in neuronal dysfunction and cell death (1). Genome-wide association studies (GWAS) have identified a cohort of risk genes associated with late-onset AD (LOAD), including, but not limited to, APOE, BIN1, SORL1, TREM2, EphA1, MEF2C, CLU, and HLA-DRB1 (2,3).
 
APOE has three allele variants: ApoE2, ApoE3, and ApoE4. ApoE4 is associated with an increased risk of AD. Evidence suggests that this risk occurs through promotion of amyloid-beta plaque aggregation (1). ApoE4 is also associated with impaired microglial response, lipid transport, synaptic integrity and plasticity, glucose metabolism, and cerebrovascular integrity (4). Mutations in BIN1, primarily involved in endocytosis and maintaining cytoskeletal integrity in the brain, are suggested to play a role in the aggravation of tau pathology (5,6). Increased levels of BIN1 have been seen in AD postmortem brain tissue (6). SORL1 expression is decreased in the brain of AD patients (7). Studies have demonstrated a role for SORL1 as a neuronal sorting receptor that binds amyloid precursor protein (APP) and regulates its trafficking and proteolytic processing, thus regulating β-amyloid (Aβ) peptide production (8). The triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor that is expressed on the cell surface of microglia, macrophages, osteoclasts, and immature dendritic cells (9). Research studies using AD mouse models indicate that deficiency and haploinsufficiency of TREM2 can lead to increased Aβ accumulation due to dysfunctional microglia response (10). EphA1 is a member of the ephrin family of receptor tyrosine kinases responsible for regulating cell morphology and motility (11). In the central nervous system (CNS), EphA1 plays a role in synaptic plasticity and axon guidance (12). EphA1 is involved in inflammatory signaling pathways (13), which may mean it plays a role in regulation of neuroinflammatory processes in AD (14). MEF2C is a member of the myocyte enhancer factor 2 (MEF2) family of transcription factors shown to play a role in learning and memory formation through regulation of synaptic plasticity (15). Studies have shown that MEF2C may play a role in age-related microglial activation through IFN-I associated MEF2C deregulation (16,17). MEF2C may also act as a modulator for APP proteolytic processing of Aβ (18,19). Clusterin (CLU) is a multifunctional glycoprotein shown to play a protective role in AD by sequestering Aβ40 peptides to form long-lived, stable complexes, which prevent amyloid fibril formation (20-22). Major histocompatibility complex class II (MHC class II) molecules are transmembrane glycoproteins expressed on the surface of antigen-presenting cells that bind exogenous peptide antigens derived from endocytosed extracellular proteins digested in the lysosome (23,24). Increases in MHC class II-expressing microglia have been shown in AD brain (25).

1. Selkoe, D.J. (2001) Physiol Rev 81, 741-66.
2. Jansen, I.E. et al. (2019) Nat Genet 51, 404-413.
3. Zhang, Q. et al. (2020) Nat Commun 11, 4799.
4. Yamazaki, Y. et al. (2019) Nat Rev Neurol 15, 501-518.
5. Franzmeier, N. et al. (2019) Nat Commun 10, 1766.
6. Chapuis, J. et al. (2013) Mol Psychiatry 18, 1225-34.
7. Scherzer, C.R. et al. (2004) Arch Neurol 61, 1200-5.
8. Andersen, O.M. et al. (2005) Proc Natl Acad Sci U S A 102, 13461-6.
9. Colonna, M. (2003) Nat Rev Immunol 3, 445-53.
10. Wang, Y. et al. (2015) Cell 160, 1061-71.
11. Yamazaki, T. et al. (2009) J Cell Sci 122, 243-55.
12. Lai, K.O. and Ip, N.Y. (2009) Curr Opin Neurobiol 19, 275-83.
13. Ivanov, A.I. and Romanovsky, A.A. (2006) IUBMB Life 58, 389-94.
14. Villegas-Llerena, C. et al. (2016) Curr Opin Neurobiol 36, 74-81.
15. Rashid, A.J. et al. (2014) Genes Brain Behav 13, 118-25.
16. Xue, F. et al. (2021) Neurobiol Dis 152, 105272.
17. Deczkowska, A. et al. (2017) Nat Commun 8, 717.
18. Tang, S.S. et al. (2016) Oncotarget 7, 39136-39142.
19. Camargo, L.M. et al. (2015) PLoS One 10, e0115369.
20. Yerbury, J.J. et al. (2007) FASEB J 21, 2312-22.
21. Narayan, P. et al. (2011) Nat Struct Mol Biol 19, 79-83.
22. Desikan, R.S. et al. (2014) JAMA Neurol 71, 180-7.
23. Ting, J.P. and Trowsdale, J. (2002) Cell 109 Suppl, S21-33.
24. Cresswell, P. (1994) Annu Rev Immunol 12, 259-93.
25. Perlmutter, L.S. et al. (1992) J Neurosci Res 33, 549-58.

Pathways & Proteins

Explore pathways + proteins related to this product.

Select Your Pathway/Protein AMPK Signaling B Cell Receptor Signaling ESC Pluripotency and Differentiation ErbB/HER Signaling Microtubule Dynamics Regulation of P38 MAPKs Translation: eIF4E and p70S6K Tyrosine Kinases & Substrates Wnt/ß-Catenin Signaling mTOR Signaling Protein: O00499 Protein: P01911 Protein: P02649 Protein: P02649_VAR_000652 Protein: P04440 Protein: P10909 Protein: P21709 Protein: Q06413 Protein: Q92673 Protein: Q9NZC2

Database Links

UniProt ID: P21709 , P02649 , Q92673 , P10909 , O00499 , P01911 , Q06413 , Q9NZC2 , P04440 , P02649_VAR_000652

Entrez-Gene Id: 2041 , 348 , 6653 , 1191 , 274 , 3123 , 4208 , 54209 , 3115

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