Blood-based biomarkers for Alzheimer disease and pre-analytical variation Flashcards

1
Q

Name 4 fluid biomarkers that can be reliably measured in CSF and blood.

A
  • Amyloid beta
  • Phosphorylated tau
  • Neurofilament light chain
  • Glial fibrillary acidic proteins (GFAP)
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2
Q

What can plasma markers like amyoid beta, GFAP and NfL predict?

A

Plasma markers can predict abnormal amyloid PET

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3
Q

What can GFAP and NfL predict in patients with subjective cognitive decline (SCD)?

A

Clinical progression

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4
Q

Which biomarker is specifically increased in AD?

A

pTau181

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5
Q

What are advantages and disadvantages of the use of CSF biomarkers?

A

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

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6
Q

What are advantages and disadvantages of the use of blood-based biomarkers?

A

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

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7
Q

What is pre-analytical variation caused by?

A

By factors that operate during research preparation prior to sampling, sample collection, processing and storage prior to measurements.

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8
Q

What factors can cause pre-analytical variation?

A
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9
Q

Think of specific examples that affect pre-analytical variation.

A
  • 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
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