Antibodies for Alzheimer’s Disease - FocusOn 130

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia that generally initiates with subtle failure of memory, progressing over years to an incapacitating level. Approximately 25 % of all AD is familial of which approximately 95 % is late-onset (age >60-65 years) and 5 % is early-onset (age

The generation of the Amyloid-β (Aβ) peptide through the proteolytic processing of the Amyloid precursor protein (APP) is a central event in the pathogenesis of AD. Extracellular accumulation of Aβ leads to formation of aggregates, fibrils and eventually amyloid deposits called neuritic plaques, a hallmark of AD. The Aβ peptide has neurotoxic effects and AD research has been focused on determining the underlying mechanisms of Aβ protein toxicity.


Fig. 1

Fig. 2
Fig. 1: Human Alzheimer’s brain stained with APP antibody Cat.-No. AP15346PU-N
Fig. 2: Immunoblot analysis with Aβ 1-40 Cat.-No. AM00001PU-N (left panel), Aβ 1-42 Cat.-No. AM00003PU-N (middle panel) and Aβ 1-43 Cat.-No. AM00004PU-N (right panel)(lane 1: Aβ 1-40; lane 2: Aβ 1-42; lane 3: Aβ 1-43)

Established candidates for the cleavage of APP to Aβ are the β-secretases BACE1 and BACE2 and Presenilin 1 and 2, which resemble the catalytic subunit of the γ-secretase complex . PEN2 (presenilin enhancer 2) is the regulatory component of the γ-secretase complex.

Fig. 3: Presenilin-1 antibody Cat.-No. AP15743PU-N staining of human brain (left). In WB Presenilin 1 antibody Cat.-No. AP13205PU-N was used with mouse kidney tissue lysate (lane 1) and HL60 cell lysate (lane 2)

Ubiquilin 1 (UBQLN1) is a ubiquitin-like protein, which has been shown to play a central role in regulating the proteasomal degradation of various proteins, including the presenilins. A role for UBQLN1 steady-state levels in affecting APP trafficking and processing has been proposed, thereby influencing the generation of Aβ.


Fig. 4

Fig. 5
Fig. 4: Western blot analysis of APPBP1 antibody Cat.-No. AP13994PU-N in CEM cell line lysates
Fig. 5: Western blot analysis of APPBP2/PAT1 antibody (center) Cat.-No. AP13998PU-N in HL60 cell line lysates

Amyloid protein-binding protein 1 (APPBP1) and Amyloid protein-binding protein 2 (APPBP2) interact with APP and are functionally associated with APP transport and/or processing.

Three alleles for Apolipoprotein E (ApoE) are known and there is a strong association of one or two copies of the ApoE allele e4 with late-onset AD, although the mechanism by which this allele impacts AD remains unproven.

Fig. 6: Detection of ApoE using Cat.-No. AP16344PU-N in human liver tissue (FFPE) (left) and with Western blot of human brain lysate (right)

Apolipoprotein E receptor 2 (ApoER2) is a member of the LDL receptor family that is highly expressed in the brain. It has been shown that ApoER2 expression stimulates Aβ production by enhanced β- and γ-secretase mediated amyloidogenic processing.

Fig.7: Lung, respiratory epithelium (FFPE) stained with ApoER2 antibody Cat.-No. AP07359PU-N

Clusterin/apolipoprotein J (Apo J) has also been identified as a potential risk gene in AD. Elevated protein levels are found in the CNS under some neuropathological conditions, such as AD, where Apo J is associated with Aβ plaques.

Microtubule-associated protein tau (MAPT/Tau) is a neuronal microtubule associated protein and it promotes tubulin polymerization and stabilizes microtubules. In its hyperphosphorylated form, tau is the major component of paired helical filaments and neurofibrillary lesions in AD brain. Hyperphosphorylation impairs the microtubule binding function of tau, resulting in the destabilization of microtubules in AD brains, ultimately leading to the degeneration of the affected neurons.

Fig. 8: Paraffin sections of human breast carcinoma stained with MAPT/TAU antibody Cat.-No. AM09107PU-N

Cyclin-dependent kinase 5 activator 1 (CDK5R1) activates CDK5, which is required for proper development of the central nervous system. CDK5R1 is cleaved from a p35 into a p25 form and has been shown to accumulate in neurons of patients with AD. This accumulation correlates with an increase in CDK5 activity and may lead to aberrantly phosphorylated forms of MAPT/TAU, which contributes to AD.

Alpha 1-antichymotrypsin (ACT) has been shown to promote Aβ polymerization and levels of ACT protein in plasma and cerebrospinal fluid from Alzheimer‘s patients have been found to correlate with progression of dementia. ACT may lead to hyperphosphorylation of tau thereby enhancing degeneration of neurons.

Fig.9: Human tonsil (FFPE) stained with ACT antibody Cat.-No. AP15343PU-N

Calsenilin and KCNIP1/VABP are members of the family of voltage-gated potassium channel-interacting proteins. They interact with presenilin 1 and 2 and are implicated in the mediation of Aβ formation.

Brain-derived neurotrophic factor (BDNF) belongs to so-called neurotrophins and supports the survival of existing neurons and encourages the growth and differentiation of new neurons. Neurotrophins are thought to have a protective role against Aβ toxicity.

Detection of Neurofilament M can be used in studies to visualize neurofilament accumulation as it can be seen in AD.

Fig.10: Immunofluorescence staining of neurofilament M in murine Neuro2A cells (red, DNA stained by Hoechst (blue)) and WB analysis of neurofilament M in porcine brain lysate (reducing conditions) with Cat.-No. SM3068P

In AD, microglial expression of Macrophage scavenger receptor 1 ( MSR1/CD204) is increased. Findings of CD204 mediated adhesion and endocytosis of fibrillar Aβ by microglia and astrocytes suggest a role for this receptor in neuronal homeostasis and neuropathology.

Il-1 is a cytokine which is overexpressed in the AD brain. This correlates to plaque formation and progression by leading to excessive expression of neuronal APP and other plaque-associated proteins and to nonsensical growth of dystrophic neuritis. Polymorphism in the IL-1A and IL-1B genes are discussed for early age onset AD.

Fig.11: Immunofluorescence staining of mouse carotid artery tissue (cryo sections) with IL-1B antibody Cat.-No. R1191P (red). Tissue was counterstained with bisbenzimide solution. A) shows no IL-1B staining of WT uninjured mouse carotid tissue. B) shows IL-1B staining of cells after surgical injury of tissue. C) shows no IL-1B staining of injured carotid tissue from an IL-1B KO mouse

Kallikrein-6 is a serin protease and abnormal levels have been found in patients with AD. The potential role of Kallikrein-6 as a biomarker for AD is under investigation and it has been reported that this protein might play a role in the degradation of Aß or turnover of APP.

Homeobox protein MOX-2 (MEOX2) is a regulator of vascular differentiation and its expression is low in AD. It has been shown that restoring expression of the protein stimulates angiogenesis, suppresses apoptosis and increases the levels of a major Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP), at the blood-brain barrier.

Bax, a pro-apoptotic protein belonging to the Bcl-2 family, promotes increased apoptosis leading to enhanced neuronal degeneration in progression of AD. Bax may play a similar role in Huntington's disease.

Fig. 12: Paraffin sections of human normal breast tissue stained with Bax antibody Cat.-No. AM11090PU-S

Humanin and its homologue in rats, Rattin, have been shown to suppress the onset of AD-related dementia by inhibiting both AD-related neuronal cell death and dysfunction. Humanin diminishes aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and competitively inhibiting the binding of APP to the formyl peptide receptor-like-1 (FPRL1).

While in AD there is abundant evidence for the involvement of oxidative stress, the cause or the consequences are largely unresolved. NAD(P)H dehydrogenase (quinone 1) (NQO1), a redox-regulated flavoenzyme, plays a central role in monitoring cellular redox state and has been shown to be increased in AD.

Recent studies reveal complement component (3b/4b) receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein (PICALM) as potential risk genes in AD. Results for CR1 indicate a role in the clearance of Aβ, but the importance of CR1 and PICALM proteins in AD remains to be elucidated.

 

Key References

 
Carrión, AM, 1998, Mol Cell Biol
 
Corneveaux, JJ, 2010, Hum Mol Genet
 
Fuentealba, RA, 2007, Mol Neurodegener
 
Hiltunen, M, 2006, J Biol Chem
 
Husemann, J, 2002, Glia
 
Lambert, J, 2009, Nat Genet
 
Matsuoka, M, 2010, Mol Neurobiol
 
Mrak, RE, 2001, Neurobiol Aging
 
Ogawa, K, 2000, Psychiatry Clin Neurosci
 
Padmanabhan, P, 2006, Brain
 
Raina AK, 1999, Redox Rep
 
Smith, FP, 2005, Nat Med
 
Studzinski, GP and Harrison JS, 2003, Leuk Lymphoma

 

Further readings

See the PDF-version: FocusOn 130

Please refer also to other FocusOns in this series about Neurosciences

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Antibodies

Catalog No. Host Iso. Clone Pres. React. Applications  
AP15343PU-N

Alpha-1-antichymotrypsin (ACT) antibody

Human tonsil stained with Anti-ACT antibody (AP15343PU) Rabbit Purified Hu P, WB
1 ml / $330.00
    Acris Antibodies GmbH
AP15343PU-S

Alpha-1-antichymotrypsin (ACT) antibody

Human tonsil stained with Anti-ACT antibody (AP15343PU) Rabbit Purified Hu P, WB
0.1 ml / $235.00
    Acris Antibodies GmbH
BM4062

Alpha-1-antichymotrypsin (ACT) antibody

BM4062 ACT antibody staining of Human Tonsil Paraffin Section. Mouse IgG1 ACT14C7 Aff - Purified Hu C, P
0.2 mg / $360.00
    Acris Antibodies GmbH
AM00001BT-N

Amyloid beta (1-40) antibody

Immunoblot Analysis: Amyloid beta A4 peptides were applied on SDS-PAGE and transferred to a PVDF membrane. The immunoblot was probed with 2µg/ml mab bA4 (40)-5C3 for 1h at 15-22°C and developed by ECL (exposure time: 30 sec). 
Lane 1: bA4 (1-40)
Lane 2: bA4 (1-42)
Lane 3: bA4 (1-43) Mouse IgG1 5C3 Biotin Hu E, ICC/IF, WB
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00001FC-N

Amyloid beta (1-40) antibody

Amyloid beta Mouse IgG1 5C3 FITC Hu ICC/IF
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00001PU-N

Amyloid beta (1-40) antibody

Immunoblot Analysis: Amyloid beta A4 peptides were applied on SDS-PAGE and transferred to a PVDF membrane. The Immunoblot was probed with 2 µg/ml mab bA4 (40)-5C3 for 1h at 15-22°C and developed by ECL (exposure time: 30 sec). 
Lane 1: bA4 (1-40), Lane 2: bA4 (1-42), Lane 3: bA4 (1-43) Mouse IgG1 5C3 Purified Hu E, ICC/IF, WB
0.1 mg / $430.00
    Acris Antibodies GmbH
AM00003BT-N

Amyloid beta (1-42) antibody

Immunoblot Analysis: Amyloid beta A4 peptides were applied on SDS-PAGE and transferred to a PVDF membrane. The immunoblot was probed with 2µg/ml mab bA4 (42)-8G7 for 1h at 15-22°C and developed by ECL (exposure time: 30 sec).
Lane 1: bA4(1-40)  
Lane 2: bA4 (1-42)  
Lane 3: bA4 (1-43) Mouse IgG1 8G7 Biotin Hu E, ICC/IF, WB
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00003FC-N

Amyloid beta (1-42) antibody

Amyloid beta Mouse IgG1 8G7 FITC Hu ICC/IF
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00003PU-N

Amyloid beta (1-42) antibody

Figure 1. Immunoblot Analysis Amyloid beta A4 peptides: Lane 1: bA4(1-40), Lane 2: bA4 (1-42), Lane 3: bA4 (1-43) were applied on SDS-PAGE and transferred to a PVDF membrane. The Immunoblot was probed with 2 µg/ml mab bA4 (42)-8G7for 1h at 15-22°C and developed by ECL (exposure time: 30 sec). Mouse IgG1 8G7 Purified Hu E, ICC/IF, WB
0.1 mg / $430.00
    Acris Antibodies GmbH
AM00004BT-N

Amyloid beta (1-43 specific) antibody

Amyloid beta Mouse IgG1 6G12 Biotin Hu E, WB
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00004PU-N

Amyloid beta (1-43 specific) antibody

Immunoblot Analysis: Amyloid beta A4 peptides (lane 1: bA4(1-40); lane 2: bA4 (1-42); lane 3: bA4 (1-43)) were applied on SDS-PAGE and transferred to a PVDF membrane. The immunoblot was probed with 2 µg/ml AM00004PU-N for 1h at 15-22°C and developed by ECL (exposure time: 30 sec). Mouse IgG1 6G12 Purified Hu E, WB
0.1 mg / $430.00
    Acris Antibodies GmbH
AM00005PU-N

Amyloid beta (free N-term, not APP reactive) antibody

Amyloid beta Mouse IgG1 11H3 Purified Hu E, WB
0.1 mg / $430.00
    Acris Antibodies GmbH
AM00006BT-N

Amyloid beta (free N-term, APP reactive) antibody

Amyloid beta Mouse IgG1 19H5 Biotin Hu E, WB
0.1 mg / $500.00
    Acris Antibodies GmbH
AM00006PU-N

Amyloid beta (free N-term, APP reactive) antibody

Immunoblot Analysis: Amyloid beta A4 peptides (lane 1: bA4(1-40); lane 2: bA4 (1-42); lane 3: bA4 (1-43)) were applied on SDS-PAGE and transferred to a PVDF membrane. The immunoblot was probed with 2µg/ml mab bA4N-19H5 for 1h at 15-22°C and developed by ECL (exposure time: 30 sec). Mouse IgG1 19H5 Purified Hu E, WB
0.1 mg / $430.00
    Acris Antibodies GmbH
AP15346PU-N

Amyloid beta A4 protein / APP antibody

AP15346PU Amyloid beta antibody staining of Human Alzheimer's Brain. Rabbit Purified Hu IP, P, WB
1 ml / $370.00
    Acris Antibodies GmbH
AP15346PU-S

Amyloid beta A4 protein / APP antibody

AP15346PU Amyloid beta antibody staining of Human Alzheimer's Brain. Rabbit Purified Hu IP, P, WB
0.1 ml / $235.00
    Acris Antibodies GmbH
AP15347PU-N

Amyloid beta A4 protein / APP antibody

Human Alzheimer’s brain stained with anti-APP antibody Rabbit Purified Hu, Ms, Rt P, WB
1 ml / $440.00
    Acris Antibodies GmbH
AP15347PU-S

Amyloid beta A4 protein / APP antibody

Human Alzheimer’s brain stained with anti-APP antibody Rabbit Purified Hu, Ms, Rt P, WB
0.1 ml / $235.00
    Acris Antibodies GmbH
AM09000PU-N

Amyloid beta A4 protein / APP antibody

Western blot analysis on Mouse brain: Tissue lysates of mouse brain (30 µg) were resolved by SDS-PAGE, transferred to NC membrane and probed with anti-human APP antibody (1/1000). Proteins were visualized using a goat anti-mouse secondary antibody conjugated to HRP and an ECL detection system. Mouse IgG2b J4H9 Purified Hu, Ms E, P, WB
0.1 ml / $350.00
    Acris Antibodies GmbH
AM09000PU-S

Amyloid beta A4 protein / APP antibody

Western blot analysis on Mouse brain: Tissue lysates of mouse brain (30 µg) were resolved by SDS-PAGE, transferred to NC membrane and probed with anti-human APP antibody (1/1000). Proteins were visualized using a goat anti-mouse secondary antibody conjugated to HRP and an ECL detection system. Mouse IgG2b J4H9 Purified Hu, Ms E, P, WB
50 µl / $255.00
    Acris Antibodies GmbH

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