Olink

Olink®
Part of Thermo Fisher Scientific

NEUROLOGY

Gene
APP

Uniprot
P05067

Protein
Amyloid-beta precursor protein

See alternative names Beta-secretase C-terminal fragment,
Beta-APP40,
Alpha-secretase C-terminal fragment,
Amyloid intracellular domain 59,
Gamma-CTF(59),
Amyloid intracellular domain 57,
Beta-APP42,
PreA4,
Cerebral vascular amyloid peptide,
Amyloid-beta A4 protein,
Amyloid precursor protein,
Alzheimer disease amyloid protein,
APPI,
ABPP,
Protease nexin-II,
Amyloid intracellular domain 50,
Gamma-CTF(57),
Gamma-CTF(50)

Uniprot Function Description

N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.

Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.

Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.

Sample type

Human EDTA plasma and serum are the recommended sample types. Human citrate plasma and heparin plasma are also accepted. For other samples types e.g cerebrospinal fluid, (CSF), tissue or cell lysates please we recommend Olink Target 96 panels. Please note that protein expression levels are expected to vary in different sample types and certain assays may be affected by interfering substances such as hemolysate.

Precision

Precision (repeatability) is calculated from linearized NPX values over LOD.

Within run precision Coefficient of Variation (CV)
5%
Between run precision Coefficient of Variation (CV)
7%

Analytical measuring range

The technical data reported below refers to the measured value in the in vitro validation assays run using known concentrations of recombinant antigen. Please note that these figures are for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples.

LOD (pg/mL)
195.3
LLOQ (pg/mL)
390.6
ULOQ (pg/mL)
200000
Hook (pg/mL)
400000
Range (logs)
2.7

Dilution factor

For optimal assay readout, Olink Explore is run using different dilutions of the original samples (undiluted, 1:10, 1:100 or 1:1000). The dilution factor for this assay is noted below and should be taken into account when estimating the appropriate addressable biological concentration of the protein based on the in vitro validation data.

Dilution factor
1:100

Sensitivity plot

The calibrator curve shown below visualizes the analytical measuring range data based on in vitro measurement of recombinant antigen. Please note that this is shown for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples. The vertical dotted lines represent LLOQ and ULOQ respectively, and the horizontal line indicates the LOD.

10⁻⁶10⁻⁴10⁻²10⁰10²10⁴10⁶10⁸1614121086420−2pg/mLNPXReplicate4PLLODLLOQULOQ

Sample distribution plot

The plot below shows the levels of protein measured in a number of commercial plasma samples. Healthy subjects are shown in blue and samples obtained from patients with a range of diseases are shown in red. The latter include inflammatory, cardiovascular, autoimmune & neurological diseases, as well as cancer. The data is shown to give a general idea of the sort of data range to expect, but cannot cover all potential levels that may be seen in clinical samples.

1614121086420−2NPXControl SamplesDisease Samples

Biomarker Validation Data

Additional validation data, as well as a more detailed description of how the Olink panels are quality controlled can be found in our Data Validation documents – go to Document download center

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