Blood-based biomarkers for Alzheimer disease and pre-analytical variation Flashcards
Name 4 fluid biomarkers that can be reliably measured in CSF and blood.
- Amyloid beta
- Phosphorylated tau
- Neurofilament light chain
- Glial fibrillary acidic proteins (GFAP)
What can plasma markers like amyoid beta, GFAP and NfL predict?
Plasma markers can predict abnormal amyloid PET
What can GFAP and NfL predict in patients with subjective cognitive decline (SCD)?
Clinical progression
Which biomarker is specifically increased in AD?
pTau181
What are advantages and disadvantages of the use of CSF biomarkers?
Advantage:
- Widely established sample type for the analysis of ND
- Communicates directly with the brain via interstitial fluid around the brain
- Less turnover and protease activity
Disadvantage:
- Studies show that lumbar punctures are often viewed negatively
- Clinicians may consider lumber punctures to be a complicated and time-consuming procedure
What are advantages and disadvantages of the use of blood-based biomarkers?
Advantage:
- Blood communicates with the brain via lymph vessels and through the glymphatic system
- Easily accessible, routine testing, less invasive
Disadvantage:
- Less direct interchange than CSF
- Biomarker has to cross the BBB and concentrations are even lower than in CSF
- Pre-analytical variations more prominent in blood than CSF
What is pre-analytical variation caused by?
By factors that operate during research preparation prior to sampling, sample collection, processing and storage prior to measurements.
What factors can cause pre-analytical variation?
Think of specific examples that affect pre-analytical variation.
- Type of collection tube used
- Filling height matters (e.g. half vs fully filled)
- Time of day
- Long delays (e.g. pre- or post-centrifugation delays)
- Aliquot filling height
- Tube transfers
- Temporary or longer -20 degrees celcius storage
- Time to measure