Amyloid Precursor Protein (APP) processing in Alzheimer’s ...Presenilin 1 7297 P ELISA, IHC-Fr,...
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www.abcam.com Amyloid Precursor Protein (APP) processing in Alzheimer’s Disease Follow the APP pathway for exceptional Alzheimer’s antibodies at www.abcam.com/neuroscience Raf sos P Grb2 P T B Ras MAPK Ubiquilin Mint - 2 Mint - 3 Mint - 1 Fe65 A I C D C PS1 / PS2 Pen-2 Aph - 11 Aph - 12 Aph - 1 cleavage activates - secretase - secretase - secretase - secretase ADAM10 ADAM17 BACE1 BACE2 - 40 - 42 - 49 CLAC-P Protease 2M A A A A A A Protease IDE Protease NEP Protease PLG N APP NCT OLIGOMERIZATION DEGRADATION CLEARANCE / EXPORT CYTOPLASM A P3 ApoE ApoE LUMEN SH2 Shc A A A A A A A A Y E N P T Y L R P N O T C H E r b B 4 C D 4 4 P 7 5 N T R secretase E - C A D H E R I N APP can be processed by -secretase (ADAM10/17), precluding the formation of amyloid beta (A), or by -secretase (BACE1/2). Cleavage by BACE1 and then -secretase (containing presenilin-1/2 (PS), Nicastrin, Aph-1 and Pen-2) generates A, the major component of brain plaques characterising Alzheimer's Disease. A has many fates: oligomerization and association with proteins such as CLAC-P or ApolipoproteinE (ApoE) in amyloid plaques, clearance by 2-macroglobulin (2M), ApoE, or low density lipoprotein receptor-related protein (LRP), or degradation by proteases such as insulin degrading enzyme (IDE), neprilysin (NEP) or plasminogen (PLG). Alterations in any pathway can lead to increased levels of A. APP is also involved in an intracellular signaling cascade upon phosphorylation of tyrosine 688, the C-terminus can be stabilized and linked to other proteins by interacting adaptor proteins such as the Mints or Fe65 and cleavage by -secretase releases an amyloid intracellular domain (AICD) that may affect nuclear transcription. Interactions of proteins such as presenilin (PS), with molecules such as ubiquilin, may contribute to AD. There are many other type-I integral membrane proteins that are cleaved by -secretase and the biological significance of these cleavages remain to be determined. neuroscience - APP alphabetical 28/7/05 15:57 Page 1
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www.abcam.comAmyloid Precursor Protein (APP) processing in Alzheimer’s Disease
Follow the APP pathway forexceptional Alzheimer’s antibodiesat www.abcam.com/neuroscience
Rafsos
P
Grb2
PTB
Ras
MAPK
Ubiquilin
Mint - 2 Mint - 3Mint - 1
Fe65
AICD
C
PS1 / PS2
Pen-2Aph - 1�1Aph - 1�2Aph - 1�
cleavageactivates� - secretase
� - secretase
� - secretase
� - secretase
ADAM10ADAM17
BACE1
BACE2
- 40- 42- 49
CLAC-P
Protease �2M
A�
A� A�
A�
A�
A�
Protease IDE
Protease NEP
Protease PLG
N
APP
NCT
OLIGOMERIZATION DEGRADATIONCLEARANCE / EXPORT
CYTOPLASM
A�
P3ApoE
ApoE
LUMEN
SH2
Shc
A�
A�
A�
A� A� A�
A�
A�
YENPTY
LRP
NOTCH
ErbB4
CD44
P75NTR
� secretase
E-CADHERIN
APP can be processed by �-secretase (ADAM10/17), precluding the formation of amyloid beta (A�), or by �-secretase (BACE1/2). Cleavage by BACE1 and then �-secretase (containing presenilin-1/2 (PS), Nicastrin, Aph-1 andPen-2) generates A�, the major component of brain plaques characterising Alzheimer's Disease. A� has many fates: oligomerization and association with proteins such as CLAC-P or ApolipoproteinE (ApoE) in amyloid plaques,clearance by �2-macroglobulin (�2M), ApoE, or low density lipoprotein receptor-related protein (LRP), or degradation by proteases such as insulin degrading enzyme (IDE), neprilysin (NEP) or plasminogen (PLG). Alterations inany pathway can lead to increased levels of A�. APP is also involved in an intracellular signaling cascade upon phosphorylation of tyrosine 688, the C-terminus can be stabilized and linked to other proteins by interacting adaptorproteins such as the Mints or Fe65 and cleavage by �-secretase releases an amyloid intracellular domain (AICD) that may affect nuclear transcription. Interactions of proteins such as presenilin (PS), with molecules such as ubiquilin,may contribute to AD. There are many other type-I integral membrane proteins that are cleaved by �-secretase and the biological significance of these cleavages remain to be determined.
neuroscience - APP alphabetical 28/7/05 15:57 Page 1
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Here are Abcam’s best sellingantibodies for Alzheimer’s research.We have over 275 products in thisrange to choose from.
Beta amyloid monoclonal antibodies (ab10146) and (ab1910)
Beta amyloid peptides vary in length from 39 to 43 amino acids.They are the major constituents of the plaques and tangles thatoccur in Alzheimer's disease. Antibodies to beta amyloid are goldstandard tools for elucidating the biology of Alzheimer's disease.
Beta amyloid antibodies [6E10](ab10146) and [4G8] (ab1910) workwell in immunohistochemistry usingparaffin-embedded cerebellum (as seenhere for ab10146) as well as westernblot, immunoprecipitation, ELISA &immunohistochemistry.
Recent customer publication using ab10146:� Telese et al. (2005) EMBO Reports 6, 1, 77-82
Spotlight: Top Alzheimer’s products
Amyloid Precursor Protein antibody [MABDE2B4](ab12266)
Amyloid Precursor Protein is cleaved by BACE and gamma secretaseto form beta amyloid peptides. Cleavage takes place during the lastAmyloid Precursor Protein processing step.
Amyloid Precursor Protein antibody[MABDE2B4] (ab12266) recognises anepitope near the N-terminus of beta-amyloid peptides. Immunohistochemistryof Alzheimer's temporal lobe tissueshows staining of plaques in the neuropil(circled in black). Amyloid depositsstained by ab12266 can be seen aroundsome blood vessels.
Applications tested for ab12266:� western blot � immunoprecipitation � immunocytochemistry� immunohistochemistry (formalin-fixed paraffin-embedded sections)
www.abcam.com/neuroscience
www.abcam.com
ERK1 + ERK2 4820 P FACS, IHC-Fr, WB(phospho T185 + T202) GSK3 (alpha + beta) 4797 P Dot, ELISA, WB(phospho Y216 + Y279) Tau 8763 P IHC-P, IHC-FrTau [TAU-5] 3931 M IHC-Fr, IHC-P, WBTau (phospho T181) 4748 P WBTau (phospho T205) 4841 P IHC-Fr, WBTau (phospho T212) 4842 P WBTau (phospho S262) 4856 P WBTau (phospho S356) 4857 P WBTau (phospho S396) 4858 P WBTau (phospho S404) 4860 P WBUbiquitin 6309 P IA, IF, IHC-Fr, WBUbiquitin [1B4-UB] 122 M FACS, IHC-Fr, IHC-P, WBUbiquitin [Ubi-1] 7254 M IHC-Fr, IHC-P, IP, WB
Other Alzheimer’s markersalpha 2 macroglobulin 2405 P IHC-Fr alpha 2 macroglobulin [1204] 20063 M ELISAalpha Synuclein 6162 P ICC, IHC-Fr, IHC-P, WBalpha Synuclein [4D6] 1903 M ELISA, IHC-Fr, IHC-P, WBalpha Synuclein [4B12] 1904 M ELISA, IHC-Fr, IHC-P, WBbeta Synuclein 6165 P ICC, IHC-Fr, IHC-P, WBgamma Synuclein 6169 P IHC, IHC-Fr, IHC-P, WBpan Synuclein 6176 P IHC-Fr, IHC-P, WBAls2 4155 P Fast trackALS2CR3 4200 P Fast trackApolipoprotein E 7620 P ELISA, IHC-P, WBApolipoprotein E [D6E10] 1906 M IHC-Fr, IHC-P, WBApolipoprotein E [E6D7] 1907 M IHC-Fr, IHC-P, IP, WBCalpastatin [2G11D6] 3515 M ICC, WBCalpastatin [1F7E3D10] 5582 M ICC, WBCaspase 6 2552 P WBCaspase 6 [6CSP03] 4062 M WBCCKAR 14441 P WBDrebrin 11068 P WBDrebrin [M2F6] 12350 M IHC-Fr, IHC-P, WBERAB [5F3] 10260 M IF, IHC-Fr, IHC-P, WBLow density lipoprotein [8G1] 20384 M IF, IHC, FACS, DotPlasminogen 2904 P WBUbiquilin 3341 P WB
KEY: M - Monoclonal P - Polyclonal
Target Datasheet Clonality Applicationswww.abcam.com/ab tested
AmyloidADAM10 10956 P WBAMPK alpha 1 3759 P IP, WBAmyloid Precursor Protein 12266 M ICC, IHC-P, IP, WB [MABDE2B4]Amyloid Precursor Protein 15272 P IHC-P, WBAmyloid Precursor Protein 17417 P ICC, IHC-P, IP, WB (phospho T668)APH1a 12104 P WBBeta Amyloid [6E10] 10146 M ELISA, IHC-P, IP, WBBeta Amyloid [4G8] 1910 M ELISA, IHC-P, IP, WBBeta Amyloid 1-40 10147 P ELISA, IHC-P, WBBeta Amyloid 1-42 10148 P ELISA, IHC-P, WBBeta Amyloid 1-43 [4H309] 17421 M WBBeta Amyloid 14220 P IHCBeta Amyloid 2539 P ELISA, WBFactor VIII heavy chain 6345 M ELISA, WB[RFFVIIIC/8]FE65 5668 P WBMint1 3448 P WBMint3 3450 P WBPEN2 16555 P IP, WBRAGE 7764 P ELISA, IHC-PRAGE 3611 P IHC-Fr, WBSHC (phospho Y239 + Y240) 4890 P WB
ProteasesBACE1 11028 P IHC-PBACE2 8024 P WBCathepsin H [1D10] 7432 M IHC-Fr, IHC-P, WBNicastrin 3444 P WBPresenilin 1 7297 P ELISA, IHC-Fr, IHC-P, WBPresenilin 1 [APS 11] 15456 M ELISA, IF, IHC-P, WBPresenilin 1 [APS 18] 15458 M ELISA, IF, WBPresenilin 2 7301 P ELISA, IHC-PPresenilin 2 [APS 21] 15548 M ELISA, IF, WBPresenilin 2 [APS 26] 15549 M ELISA, IF, WB
Tangles & Tau14-3-3 tau [3B9] 10439 M IP, WBCasein Kinase 1 delta 10877 P ELISA, IHC-PERK1 7947 P IHC-P, IP, WBERK1 + ERK2 3918 P WB
Target Datasheet Clonality Applicationswww.abcam.com/ab tested
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