Frame work biomarker development

Question 1

What is the definition of dementia?

Answer 1

The progressive impairment of cognitive functions (reasoning, emotional control, memory)

Question 2

Name the cause of these different forms of dementia.

Different forms of dementia are:
- Alzheimer’s Disease
- Vascular dementia
- Lewy Body dementia
- Frontotemporal dementia

Answer 2

• Alzheimer’s Disease → caused by neurofibrillary tangles (NFTs) and amyloid plaques
• Vascular dementia → caused by damaged blood vessels in the brain or interruption of the blood flow/oxygen to the brain
• Lewy Body dementia → caused by abnormal deposits of alpha-synuclein (i.e. Lewy bodies)
• Frontotemporal dementia → caused by abnormal tau or TDP-43.

Question 3

What is the value of fluid biomarkers?

Answer 3

• Diagnosis → increase diagnostic accuracy
• Prognosis → predict what will happen
• Treatment monitoring or response
• Understand the disease etiology

Question 4

There is an unmet clinical need in regard to the different forms of dementia. What is this unmet need?

Answer 4

There is an unmet need to improve differential diagnosis of dementia and to capture the full complexity of these associated mechanisms. So novel fluid biomarkers are needed to discriminate the different forms of dementia.

Question 5

The development of novel biomarkers consists of 5 different phases. Name these.

Answer 5

1. Biomarker identification
2. Initial validation
3. Retrospective longitudinal studies
4. Prospective studies
5. Implementation

Question 6

What are challenges in biomarker identification and what are solutions for this?

Answer 6

Challenges:
- Which biomarker to choose from the dataset?
- Cross-technology translation

Solutions:
- Improve selection process
- Novel technologies

Question 7

Name examples of novel technologies that can be used for the identifiction of novel biomarkers.

Answer 7

• Mass spectrometry
• Immunoassays