Topic 2 - blood biomarkers Flashcards
what is the benefit of blood based biomarkers
objective
not influenced by expectations
can’t be faked
what is the benefit of the blood brain barrier
isolates the brain from blood - brain is very sensitive to changes
what does a biomarker need to be in order to determine a brain injury
brain specific
- peripheral sources can confound results
what are the 3 biomarkers for axonal injury
tau
neurofilament light (NFL)
neurofilament heavy (NFH)
why doesn’t NFH express
hard to get across the barrier (too big)
what is NFL expression
mainly from brain (also from renal)
good correlation between levels in blood and CSF
big increase after boxing (comes down after rest)
blood (serum) levels potentially sensitive biomarker for axonal injury (not always)
what is tau expression
mainly from brain (also pancreas, kidneys, heart)
helps connect tubules and filaments (presence in blood can indicate damage)
increased tau at 6 hours can help predict a delayed return to play
what is a biomarker for white matter integrity
myelin basic protein (MBP)
what is MBP expression
not brain specific - myelin everywhere
what is the significance of the myelin water fraction
decreased up to 20 days
= less efficient myelin
- ability to communicate is still delayed in the brain up to 2 months (even if symptoms are gone)
what biomarkers show enrichment in the neuronal soma
NSE
UCH-L1
what is NSE expression
mainly brain
can come from other areas (not fully brain specific)
what is UCH-L1 expression
mainly brain
can come from other areas (not fully brain specific
shows elevation in GCS 15 - reporting as fine
- larger elevation in GCS 13/14
what do astrocytes and microglia secrete
s100B
glial fibrillary acidic protein (GFAP)
where are glial cells present
ONLY in the brain!
what is s100B expression
comes from everywhere (brain, fat, muscle, etc)
should not be used for concussion
what is GFAP expression
most specific to the brain
large increase in expression
24 hours to peak, still elevated up to 7 days after
what is the connection between GFAP and UCH-L1
UCH-L1 shows elevation above GFAP in all injuries (no concussion, head impact w no concussion, etc)
GFAP shows significant increase only in concussion group
- could indicate that UCH-L1 could be very sensitive to subtle impacts / not specific to the brain
where are tau deposits found in CTE
found at the depths of the sulci
more prominent across whole brain in stage 3/4
what is the difference in tau deposits between CTE and alzheimers
CTE = more prominent in sulci
AD = diffuse across whole brain
how does the time course effect how biomarkers could enter the blood and what tests should be done
- an initial increase may be released from injured cells
- delayed elevations may likely be a result of upregulation
- BBB integrity compromised after a single/multiple injuries
- does exercise / strenuous activity affect the biomarker levels in the blood
- do other injuries cause elevations of the biomarker
- tau decreases throughout the day (time of day for sample could matter) -UCH-L1 - dips after meal
