Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neurosurgery > Biomarkers for neurodegenerative diseases > Flashcards

Biomarkers for neurodegenerative diseases Flashcards

1
Q

General things about neurodegenerative diseases

A

Overlap in symptoms: dementia, motor
function
Long prodromal stage
Also classified as proteinopathies (proteins aggregate)
Pathogenesis not known
Are becoming more prevalent
100% sure diagnosis only at autopsy (looking at brain after death is still gold standard)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a biomarker?

A 
Parameter that can be easily measured
Underlies the disease pathology
Helps diagnose disease
Helps monitor disease progression/response to therapy
Is not too unpleasant for the patient

E.g. bloodsugar for diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sensitivity

A

ability to correctly identify all those with disease (might lead to false positives)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Specificity

A

only identify those with the disease (will lead to false negatives)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

AD prevalence

A

10-20% in population in over 65.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Most common type of AD

A

most patients (99%) have sporadic (non-genetic) form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Duration of AD

A

8-10 yrs, but can be 20-30 yrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Length of prodromal AD phase

A

10-20 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Protein aggregation in AD

A

beta-amyloid & phosphorylated tau

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

dominant theory on AD pathology

A

dominant theory: tau + beta-amyloid aggregation are toxic and lead to the other changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Clinical diagnosis based on:

A
  1. Typical clinical features (dementia, in particular memory loss)
  2. Absence of alternative explanation (i.g. infection, metabolic)
  3. Progressive nature (can’t be too progressive –> might be another disorder)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

The 3 biomarkers of AD

A

A - β amyloid deposition
T - pathologic tau
N - neurodegeneration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

2 methods to access biomarkers of AD

A

imaging and through fluids (CSF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Imaging methods to see markers of AD

A

β amyloid: Aβ positron emission tomography (PET)
pathologic tau: tau PET
neurodegeneration: MRI atrophy or FDG-PET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

First biomarker of AD in prodromal phase

A

β amyloid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

issues with FDG PET

A

accuracy of FDG PET decreases in older patients. In 60’s it’s almost 100% sensitivity, but in older it drops with 20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Tau/β amyloid tracer trade off?

A

Tau tracer is highly specific for AD, however less sensitive than amyloid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

CSF beta-Amyloid - 2 isoforms?

A

Aβ 42/40 ratio
placks are of the 42 type, but the total concentration is determined by 40 (more common)
in AD: 42 goes lower than in controls (ratio is senitive to that) - couterintuitive, but perhaps it’s becuase the aggragated version is stuck in the brain (but nobody knows why)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Measuring Tau in CFS?

A

Total vs phosphorylated Tau
Total Tau is marker of neuronal degeneration, phosphorylated tau is more for the clinical tool (diagnostic marker)
combination gives highest diagnostic certainty and is used in unclear clinical cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

In what other fluid than CSF can we measure protein aggregation?

A

In the blood

21
Q

phosphorylated tau in blood-plasma correlated with which 2 things?

A

phosphorylated tau in CSF samples and disease progression

22
Q

What are the “new” AD diagnostic criteria?

A 
ONLY using biomarkers:
beta-amyloid: pathological change
beta-amyloid + tau: AD
amyloid + tau + neurodegeneration: AD
no beta-amyloid = no AD
23
Q

Glial-types elevated in AD?

A

Astroglia and microglia

24
Q

Possible future marker to see if MCI will progress to AD or not?

A

A metabolomic called 2,4-dihydroxybutanoic acid, which is up-regulated in those who progress

25
Q

How/when is 2,4-dihydroxybutanoic acid up-regulated?

A

2,4-dihydroxybutanoic acid is up-regulated when we have cell stress and the Crebs cycle is disturbed

26
Q

3 types of miRNA that are changed in AD?

A

hsa-miRNA 135a, 125b & 146a –> their pattern is opposite in cancer

27
Q

The future of AD treatment

A

We hope to be able to treat individually based on biomarkers present (personalized treatment like we see with cancer patients)

28
Q

How do we currently diagnose PD?

A

clinical signs - you need bradykinesia, tremor and rigidity

29
Q

prodromal symptoms for PD

A

loss of smell, constipation and sleep problems.

RBD as a sleep disorder is a big one

30
Q

What is RBD?

A

A sleep disorder - patients act out their dreams (moving legs while running) - 90% of those with RBD will get PD

31
Q

Brain scan to diagnose PD

A

SPECT with ioflupane (I123-FP-CIT, or DaTSCAN)

32
Q

Difference in SPECT and PET

A

PET it sends out a positron and SPECT a gamma ray

33
Q

Issues with using SPECT to diagnose PD?

A

Slow specificity - reduced tracer uptake is also seen in those with MSA as well as PD

34
Q

Non-brain imaging to diagnose PD?

A

MIBG-SPECT (measures sympathetic activation of the heart). This method don’t respond to MSA patients and is therefore more specific than SPECT with ioflupane

35
Q

Which protein is phosphorylated and aggregated in PD?

A

alpha-synuclein

36
Q

Why is it hard to measure alpha-synuclein in CSF?

A

Because of how little alpha-synuclein there is in the CSF

37
Q

Is Oligomeric synuclein a good marker for PD?

A

No, not specific enough

38
Q

real-time quaking induced conversion (RT-QuIC)

A

Similar to PMCA - method where you amplify the aggregated alpha-synuclein by feeding the seed with “healthy/cellular” alpha-synuclein

39
Q

Why is CSF not a good tool in diagnosis?

A

It’s painful to extract

40
Q

alpha-synuclein can be found in the PNS. Which types of PNS biopsies do we take?

A

Submandibular gland biopsy
Colonic biopsy
Skin biopsy

41
Q

Effectiveness of a submandibular biopsy in PD diagnosis?

A

Not good - painful procedure and 50% of the time we don’t get the right tissue

42
Q

Effectiveness of a colonic biopsy in PD diagnosis?

A

A bit better than the submandibular biopsy - the specificity/sensitivity is supposed to be better, but it’s still unclear. Again, the biopsy is painful

43
Q

Effectiveness of a skin biopsy in PD diagnosis?

A

Highly specific (100%), about 80% sensitive - easier to obtain than the other biopsies

44
Q

How can we improve the specificity/sensitivity of a skin biopsy for PD diagnosis?

A

Combining the tissue with real-time quaking induced conversion to amplify the protein

45
Q

A PD marker other than alpha-synuclein?

A

Oxidised DJ-1 - the gene is a causative gene of a familial form of Parkinson’s disease (PARK7), but the oxidised protein is not very specific

46
Q

Current biomarkers of PD used in diagnosis?

A

Loss of smell and cardiac sympathetic denervation (as support to the clinical symptoms)

47
Q

Does protein pathology define PD?

A

the protein levels are a correlation and it’s not proven what causes what - in older individuals we see people with high protein deposits and they had no clinical symptoms
it’s also been found that those with more protein aggregation lives longer

48
Q

Take-home messages

A
  • AD is associated with beta-amyloid and tau pathology
  • PD is associated with alpha-synuclein pathology
  • Association ≠ causation
  • Protein deposits are very helpful biomarkers
  • As of now AD and PD are diagnosed clinically based on expert opinion (that can be a supported by biomarkers)
  • Diagnosis is shifting from clinical towards protein-based diagnostic tests
  • A combination of diagnostic tests will likely be required for early detection and monitoring of progression

Neurosurgery (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions