B. 30 Biomarkers

Question 1

Possible Biomarkers

Answer 1

• Blood Test
• Cerebrospinal Fluid
• Imaging: -pet, firm, retinal imaging

Question 2

Ideal biomarker

Answer 2

• timely
• affordable
• measuring process of pathology as well as response to treatment
• low risk
• low side effect

Question 3

“Omics” involved in AD Biomarker

Answer 3

• Proteomics
• genomics
• Transcriptomics
• Metabolomics
• Peptidomics

Question 4

Uses Of Biomarkers

Answer 4

• suscetibility
• prognostic
• predictive
• diagnostic

Question 5

Key Biomarker Changes in Cerebrospinal Fluid

Answer 5

• possibly best biomarker?
• protects brain and maintains cranial pressure
• maintains homeostatic regulation
• lumbar punction
• aBeta42 low in CSF in AD as increased binding occurring in brain
• high tau
• high hyperphosphorylated tau
• high accuracy in predicting AD before clinical symptoms occur
• can pick up oligomers which PET cannot
• however cannot distinguish between dementias
• abeta earliest marker but cannot tell whole story without tau

Question 6

Pros and Cons of Markers

short

Answer 6

Primary tissue:
\+where disease actually occurs
\+high concentration of target analytic
-not accessible
-or expensive imaging

CSF:
\+accesible
\+reasonable taget analytic concentration
\+successsful partially
-side effects
-easier in younger population

Blood:
\+cheaper
\+very accessible
-not accurate yet
-removed from disease centre

Question 7

Pros and Cons (Long)

Answer 7

Imaging
Structural:
-late in disease when neuronal death already occurred
-end stage of disease
-not specific as atrophy can occur in other disorders
+cheap
+can show structural difference in line with Braak stages
+cheap and easy

PET- analogue for glucose
+hyper-metabolism in AD, marked global reduction of glucose
+good measure for synaptic activity
+can help distinguish between different pathologies
-expensive
-accessibility

PET- Amyloid
+fibrilary Tangle detection
-not oligomers which are thought to be pathogenic
+helpful in understanding how amyloid evolves
+mirrors postmortem exam
-expensive

TAU Pet
+helpful for differential diagnosis as tau location specific (FTD)
+managment plan

Question 8

Blood Biomarker

Answer 8

cheap, easy accessible

• > BBB affected in AD so possibly able to target CSF proteins in blood
• biomarkers have bin found in blood but questionable study designs -> not replicable, not controlled for all variables

APP metabolism occurs everywhere- makes it not clinically significant as you don’t pick up the brain pathology
similar for tau