14-3-3 Protein, CSF (Creutzfeldt-Jakob)

Last Modified: 10/25/2021 12:07:28 PM


Medical Necessity Documentation:  
Client Notes:  
Specimen Requirements: 5.0 mL CSF in a Sterile Plastic Vial

Collection Instructions: National Prion Order Form Clinical History required to be filled out by ordering provider 


Collect CSF by lumbar puncture.
Discard first 2 mL that flows from tap.
Collect next 5 mL CSF, avoiding bloody tap.
Freeze within 20 minutes of collection.

Minimum Volume: 0.6 mL CSF on ice
Transport & Storage: Temperature/Stability: 24 hours Ambient
14 days Refrigerated 
Indefinetly days Frozen (transport) 

Freeze within 20 minutes of collection
Rejection Criteria: Hemolysis
Reference Range:

Refer to Interpretive Report

Critical Ranges:  
Test Comments:  Freeze within 20 minutes of collection. Store and transport frozen. Ship using a styrofoam container with sufficient dry ice (5 lbs/24 hours). The NPDPSC requests a urine sample for research purposes with all CSF samples if available.
Methodology: Immunoassay • RT-QuIC
Clinical Significance:

The 14-3-3 proteins are a group of highly conserved proteins composed of several isoforms that are involved in the regulation of protein phosphorylation and mitogen-activated protein kinase pathways. They exist in vivo as dimers of the various isoforms with apparent molecular mass of 30 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and 60 kDa on gel chromatography. Sequence homology among the various isoforms ranges from 22% to100%. The beta, gamma, and theta isoforms are found in tissues of the nervous system.

Detectable 14-3-3 protein in the cerebrospinal fluid (CSF) is indicative of substantial, relatively rapid neuronal destruction. Increased CSF concentrations of 14-3-3 proteins have been described in patients with various forms of Creutzfeldt-Jakob disease (CJD), some other rapidly progressive dementias, and a large range of other vascular, inflammatory, neoplastic, and metabolic central nervous system (CNS) disorders (see Cautions), which can be associated with significant and rapid neuronal destruction.

The main clinical use of 14-3-3 measurements is in the differential diagnosis of dementia, in particular to distinguish CJD and its variants from other dementias. The most common forms of dementia (progressive multi-infarct dementia and Alzheimer disease) are uncommonly associated with elevated CSF levels of 14-3-3, presumably because of their slow pace of progression.

CJD is an incurable neurodegenerative disease caused by accumulation of self-catalytically malfolded endogenous prion proteins in the CNS. Its cause is most commonly sporadic, but it can be inherited (mutations that predispose to malfolding) or acquired (iatrogenic transmission by infected human tissues or tissue extracts or surgical procedures, or by ingestion of some animal products that contain malfolded prion proteins).

The diagnosis of CJD is highly complex and involves clinical history and neurologic examination, electroencephalographs (EEG), magnetic resonance imaging (MRI), and exclusion of other possible causes of dementia, in addition to CSF examination. Several, slightly different scoring systems are in use to integrate these parameters into a final diagnosis of possible, probable, or definite CJD. The most widely accepted of these scoring systems is the WHO set of diagnostic criteria for sporadic CJD from 1998 (see Interpretation). Supporting, in conjunction with other tests, a diagnosis of Creutzfeldt-Jakob disease in patients with rapidly progressive dementia when other neurodegenerative conditions have been excluded

Documentation:  The 14-3-3 proteins are a group of highly conserved proteins composed of several isoforms that are involved in the regulation of protein phosphorylation and mitogen-activated protein kinase pathways. They exist in vivo as dimers of the various isoforms with apparent molecular mass of 30 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and 60 kDa on gel chromatography. Sequence homology among the various isoforms ranges from 22% to100%. The beta, gamma, and theta isoforms are found in tissues of the nervous system.

Detectable 14-3-3 protein in the cerebrospinal fluid (CSF) is indicative of substantial, relatively rapid neuronal destruction. Increased CSF concentrations of 14-3-3 proteins have been described in patients with various forms of Creutzfeldt-Jakob disease (CJD), some other rapidly progressive dementias, and a large range of other vascular, inflammatory, neoplastic, and metabolic central nervous system (CNS) disorders (see Cautions), which can be associated with significant and rapid neuronal destruction.

The main clinical use of 14-3-3 measurements is in the differential diagnosis of dementia, in particular to distinguish CJD and its variants from other dementias. The most common forms of dementia (progressive multi-infarct dementia and Alzheimer disease) are uncommonly associated with elevated CSF levels of 14-3-3, presumably because of their slow pace of progression.

CJD is an incurable neurodegenerative disease caused by accumulation of self-catalytically malfolded endogenous prion proteins in the CNS. Its cause is most commonly sporadic, but it can be inherited (mutations that predispose to malfolding) or acquired (iatrogenic transmission by infected human tissues or tissue extracts or surgical procedures, or by ingestion of some animal products that contain malfolded prion proteins).

The diagnosis of CJD is highly complex and involves clinical history and neurologic examination, electroencephalographs (EEG), magnetic resonance imaging (MRI), and exclusion of other possible causes of dementia, in addition to CSF examination. Several, slightly different scoring systems are in use to integrate these parameters into a final diagnosis of possible, probable, or definite CJD. The most widely accepted of these scoring systems is the WHO set of diagnostic criteria for sporadic CJD from 1998 (see Interpretation). Supporting, in conjunction with other tests, a diagnosis of Creutzfeldt-Jakob disease in patients with rapidly progressive dementia when other neurodegenerative conditions have been excluded

Custom Panel: No

PRODUCTION SCHEDULE

Turn Around Time: 2 to 6 days
Days Performed: Monday, Thursday
Sites Performed: Quest - Chantilly to National Prion Lab
PHL Test Code: CJD
EPIC Test Code: MISC
Send Out Test Code: 37989
Alternate Test Names: 14-3-3 Protein, CSF; 14-3-3 Protein, Spinal Fluid; CJD; Cretuzfeld-Jakob; Protein 14-3-3
Included Tests:  
CPT Coding: 0035U, 83520 (x2)

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