About AlzBiomarker

Glossary

To facilitate meta-analysis, AlzBiomarker uses standardized terms to refer to biomarkers, disease conditions, and assay methods. For example, within the database, the biomarker term "Aβ42" may refer to data originally reported as Aβ1-42 or Aβ42x-42, depending on the epitopes of the antibodies used. See below for brief descriptions of the terms used in the database.

Biomarkers

Aβ38: Amyloid-beta38 is a peptide product of Amyloid Precursor Protein (APP) processing.

Aβ40 Amyloid-beta40 is a peptide product of APP. Within the database, Aβ40 refers to all forms of the peptide (e.g., Aβ401-40 and Aβ40x-40) irrespective of the specific epitopes used for detection.

Aβ42: Amyloid-beta42 is a peptide product of APP. Within the database, Aβ42 refers to all forms of the peptide (e.g., Aβ421-42 and Aβ42x-42) irrespective of the specific epitopes used for detection.

albumin ratio: a ratio of albumin in cerebrospinal fluid compared to levels in a blood fraction (either serum or plasma). Thought to reflect the functioning of the blood brain barrier.

GFAP: Glial fibrillary acidic protein is a intermediate filament protein enriched in reactive astrocytes.

hFABP: Fatty acid-binding protein, heart is a lipid-binding protein expressed in the brain. Synonyms: Fatty acid-binding protein 3, FABP3, H-FABP.

MCP-1: Monocyte chemotactic protein 1 is a chemokine secreted by immune cells. It recruits monocytes and is thought to be a marker of inflammation. Synonyms: C-C motif chemokine 2.

neurogranin: a dendritic protein implicated in synaptic plasticity. CSF neurogranin is thought to reflect synaptic degeneration.

NFL: Neurofilament light polypeptide is an intermediate filament protein found in the cytoskeleton of neurons.

NSE: Neuron-specific enolase is a glycolytic enzyme enriched in neurons. Synonyms: Enolase 2, Gamma-enolase.

sAPPα: soluble Amyloid precursor protein alpha is a secreted cleavage product of Amyloid Precursor Protein (APP). Synonyms: secreted amyloid precursor protein alpha.

sAPPβ: soluble Amyloid precursor protein beta is a secreted cleavage product of Amyloid Precursor Protein (APP). Synonyms: secreted amyloid precursor protein beta.

sTREM2: soluble Triggering receptor expressed on myeloid cells 2 (sTREM2) is an ectodomain fragment released by the proteolytic processing of the microglial transmembrane protein.

tau-phospho: phosphorylated tau refers to any phosphorylated form of the microtubule-associated protein tau, including tau phosphorylated at serine 181 (p181) and threonine 231 (p231).

tau-total: total tau protein irrespective of phosphorylation state. Synonyms: microtubule-associated protein tau.

VLP-1: Visinin-like protein 1 is a neuronal calcium signaling molecule. Synonyms: VILIP-1, Hippocalcin-like protein 3.

YKL-40: Chitinase-3-like protein 1 is a glycoprotein that structurally resembles chitotriosidase and is mainly expressed in astrocytes in the brain. It is thought to be a marker of neuroinflammation.

Conditions

Alzheimer's disease (AD): Clinical Alzheimer's disease as defined by specified diagnostic criteria.

Cognitively Normal Control (CNC): A control group reported by the authors to be cognitively healthy, with or without neuropsychiatric testing.

Familial Alzheimer's disease (FAD): Individuals carrying a known causative mutation, as well as those with an inherited form of AD for which the genetic cause is unknown.

Mild Cognitive Impairment progressing to Alzheimer's disease (MCI-AD): Individuals meeting criteria for mild cognitive impairment at baseline who convert to a diagnosis of Alzheimer's dementia at a later clinical evaluation.

Mild Cognitive Impairment, stable (MCI-stable): Individuals meeting criteria for mild cognitive impairment at baseline who maintain MCI status at clinical evaluation at least two years later.

Other Controls: Individuals described as "hospital controls" and those with non-neurodegenerative diseases. Cognitive status is often unknown or not reported.

Preclinical Alzheimer's disease (Pre-AD): Individuals who were cognitively healthy at baseline but who meet diagnostic criteria for AD at a later clinical evaluation.

Preclinical Familial Alzheimer's disease (Pre-FAD): Individuals with a family history of AD who do not display cognitive symptoms at baseline.

Methods

Biochip Immunoassay: An immunoassay using a chip format to simultaneously measure multiple analytes in a sample.

Colorimetric Assay: An assay using reagents that undergo a measurable color change in the presence of the analyte. The color change correlates with the concentration of the analyte.

Electrochemiluminescence: An immunoassay using detection antibodies associated with an electrochemiluminescent label.

ELISA: A common protein analysis technique, usually conducted in a 96-well plate format, in which the antigen is stabilized on a solid surface and probed with a specific enzyme-conjugated antibody. The resulting enzymatic reaction is then measured. Traditional ELISAs use chromogenic reporters. Newer ELISA techniques use fluorogenic and electrochemiluminescent reporters which can offer higher sensitivities and the ability to simultaneously detect multiple antigens (i.e., multiplex). Although not technically ELISA, because they are not "enzyme-linked", these assays are often called ELISA due to similarities in the general assay principles. In sandwich ELISAs, a capture antibody is used to immobilize the target analyte/antigen on the solid surface.

Immunoelectrophoresis: A type of immunodiffusion technique in which a mixed protein sample is first separated by gel electrophoresis and then the individual proteins are visualized by applying specific antibodies to the gel through immunodiffusion. When levels of antigen and antibody are near equivalent, the complexes that form precipitate and are detectable as a precipitin arc.

Immunomagnetic Reduction: An immunoassay in which magnetic particles are coated with antibody and the reduction in the spin of the particles correlates with the amount of ligand bound.

Mass Spectrometry: A sensitive technique used to detect, identify, and quantify molecules based on their mass and charge (m/z) ratio.

Nephelometry: A technique to assess protein levels, by measuring the turbidity of a sample. Typically an antibody and antigen are mixed and the resulting small aggregates are detected by passing a light through the sample. The amount of light scatter is compared to a standard curve.

Radio Immunoassay (RIA): A classic quantitative immunoassay technique that uses antibodies to detect and quantitate the amount of antigen in a sample. Typically  radioactive isotopes, such as 125I or 3H, are used to label an antigen (known as a tracer or radioligand), which then competes with a non-radioactive antigen for a fixed number of antibody or receptor binding sites. Results are compared against a standard curve.

SIMOA (Single molecule array): A bead-based immunoassay in which a target analyte is captured by antibody-coated beads and then detected using an enzyme-labeled detection antibody. The detection reaction is compartmentalized in femtoliter microwells, which may allow for a single analyte readout.

Single Molecule Counting Immunoassay: An immunoassay using fluorescent antibodies to label biomolecules and magnets to drive the molecules through a photon detector.

SRM (Selected Reaction Monitoring): A targetted mass spectrometry technique for the detection and quantification of specific predetermined analytes with known fragmentation properties.

xMAP: A bead-based multiplex immunoassay patented by the Luminex Corporation that allows for the detection of multiple analytes in a sample through the use of antibody-labeled microspheres with different spectral properties. Synonyms: xMAP (multi-analyte profiling).