Topic 2 - blood biomarkers

Question 1

what is the benefit of blood based biomarkers

Answer 1

objective
not influenced by expectations
can’t be faked

Question 2

what is the benefit of the blood brain barrier

Answer 2

isolates the brain from blood - brain is very sensitive to changes

Question 3

what does a biomarker need to be in order to determine a brain injury

Answer 3

brain specific
- peripheral sources can confound results

Question 4

what are the 3 biomarkers for axonal injury

Answer 4

tau
neurofilament light (NFL)
neurofilament heavy (NFH)

Question 5

why doesn’t NFH express

Answer 5

hard to get across the barrier (too big)

Question 6

what is NFL expression

Answer 6

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)

Question 7

what is tau expression

Answer 7

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

Question 8

what is a biomarker for white matter integrity

Answer 8

myelin basic protein (MBP)

Question 9

what is MBP expression

Answer 9

not brain specific - myelin everywhere

Question 10

what is the significance of the myelin water fraction

Answer 10

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)

Question 11

what biomarkers show enrichment in the neuronal soma

Answer 11

NSE
UCH-L1

Question 12

what is NSE expression

Answer 12

mainly brain
can come from other areas (not fully brain specific)

Question 13

what is UCH-L1 expression

Answer 13

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

Question 14

what do astrocytes and microglia secrete

Answer 14

s100B
glial fibrillary acidic protein (GFAP)

Question 15

where are glial cells present

Answer 15

ONLY in the brain!

Question 16

what is s100B expression

Answer 16

comes from everywhere (brain, fat, muscle, etc)
should not be used for concussion

Question 17

what is GFAP expression

Answer 17

most specific to the brain
large increase in expression
24 hours to peak, still elevated up to 7 days after

Question 18

what is the connection between GFAP and UCH-L1

Answer 18

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

Question 19

where are tau deposits found in CTE

Answer 19

found at the depths of the sulci
more prominent across whole brain in stage 3/4

Question 20

what is the difference in tau deposits between CTE and alzheimers

Answer 20

CTE = more prominent in sulci
AD = diffuse across whole brain

Question 21

how does the time course effect how biomarkers could enter the blood and what tests should be done

Answer 21

• 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