Brainscape's Knowledge GenomeTM

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


See full index

markers xxx > week 9 part 2 > Flashcards

week 9 part 2 Flashcards

1
Q

What does neuroimaging provide?

A

Immediate structural and functional information on the brain

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

What is Neuroimaging helpful in?

A

Predicting and monitoring disease progression

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

In relation to AD, what can neuroimaging detect?

A

specific protein and aggregates (e.g. amyloid plaques and tau tangles)

provide insight into brain structure and physiology

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

What are examples of Neuroimaging biomarkers for PET?

A
  1. Amyloid PET
  2. Tau PET
  3. [18F]-fluorodeoxyglucose (FDG) PET
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are examples of neuroimaging biomarkers for MRI?

A
  1. Structural MRI

2. Functional MRI

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

What was the first PET ligand to selectively visualise amyloid?

A
  1. [11C]-labelled Pittsburgh compound B (PiB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the half-life of [11C]-PiB?

A

20 minutes

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

What does the half-life of [11C]-PiB limits its use to?

A

Imaging centres with onsite capability to synthesise this radiotracer

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

What does Amyloid PET ligand highlight the need for?

A
  1. [18F]-ligands to make amyloid PET imaging broadly available
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a problem with PiB?

A

Radiotracer can only be synthesised/performed where the 11C-labelled Pittsburgh compound B is synthesised

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

What is Florbetapir F 18?

A

(PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does Quantitative and visual assessment of amyloid PET reveal?

A

Consistent pattern of ligand retention that replicates sequence of AB deposition found in post-mortem studies of patients with Alzheimer’s disease e.g. posterior cingulate cortex

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

Where is the Amyloid PET deposition pattern found?

A

medial temporal lobe before spreading to other regions of the cortex

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

What does amyloid PET scan show?

A

ab is consistently deposited in posterior cingulate cortex

one of the earliest region of brain is the posterior cingulate cortex

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

What does posterior cingulate cortex have?

A

number of connections with other regions- has reciprocal connections with hippocampus which is associated with learning and memory

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

What does first-generation tau PET traces include?

A
  1. [11C]-pyridinyl-butadienyl-benzotiazole 3 [PBB3]
  2. [18f]- fLORTAUCIPIR
  3. [18F] -THK5351
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does tracers have?

A

A range of off target actions

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

Where does a number of Tau tracers bind?

A

Regions of:

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

What do a number of PET tracers bind to?

A
  1. Monoamine oxidase B in Basal Ganglia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What can staining hinder?

A

Interpretation of the final image

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What leads to second generation of tau pet tracers?

A

Off-target binding events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What have Pharmaceutical companies been trying to impove?

A

Binding selectivity and pharmacokinetic profile of tau PET tracers

e.g. [18F]-MK-6240

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where was off-target binding of [18F]-MK-6240 not observed?

A
  1. Basal Ganglia

2. Choroid plexus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What was observed in substantia nigra and meninges?

A

mild tracer retention

25
Q

What has [18F]-FDG PET been used to measure?

A

measure cerebral metabolic rates of glucose (CMRglc), which is a proxy for neuronal activity

26
Q

What is [18F]-FDG PET helpful in?

A

distinguishing control patients from Alzheimer’s disease patients.

27
Q

What is metabolic activity linked to?

A
  1. neuronal activity

2. which is linked to neuronal cell death

28
Q

What does cerebral metabolic rates of glucose reduction on FDG-PET precede?

A

the onset of symptoms in predisposed individuals, in both genetic early-onset and late-onset Alzheimer’s disease.

29
Q

Where is a lack of metabolic activity seen in?

A
  1. posterior cingulate cortex
  2. Lateral temporal lobe
  3. Frontal lobes
30
Q

What has MRI been widely used for?

A

Early detection and diagnosis of AD

31
Q

Where does atrophy typically start in?

A
  1. Medial temporal and limbic areas
  2. spread to parietal association areas
  3. Frontal and primary cortices
32
Q

What does structural imaging provide?

A

anatomical information of the brain

33
Q

What does functional imaging provide?

A

Physiological processes that underscore neural activity

34
Q

What are advantages of Neuroimaging?

A
  1. Non-invasive
  2. Provides immediate structural and functional details of the brain
  3. Can reveal disease progression
35
Q

What are disadvantages to Neuroimaging?

A
  1. Expensive
  2. Requires experienced personnel
  3. Sensitivity and specifity to Alzheimer’s disease is not satisfactory
36
Q

What is the first to change in AD?

A
  1. CSF amyloid beta 42
37
Q

What are GWAS?

A

hypothesis free methods to identify associations between genetic regions (loci) and traits.

38
Q

What does a typical GWAS study collect?

A

data to find out the common variants in a number of individuals with and without a common trait across the genome using genome wide SNP arrays.

39
Q

Variants associated with the disease

A

found at a higher frequency in cases than controls.

40
Q

What is statistical analysis carried out to indicate?

A

how likely a variant is to be associated with a trait

41
Q

What are number of genes associated with AD?

A
  1. CLU
  2. PICAM
  3. CR1
42
Q

What is the strongest risk factor gene for late onset of AD?

A

APOE

43
Q

Gene-based biomarkers for AD?

A

♣ They were also able to see an association between two genes this was CLU and PICALM
♣ They were also able to see an association between two genes this was CLU and PICALM

44
Q

What does CLU gene encode for?

A

Clusterin

45
Q

What is clusterin?

A

highly conserved glycoprotein that functions primarily as an extracellular chaperone

46
Q

What has Clusterin level shown to be?

A

elevated in Alzheimer’s disease, but how the protein affects pathogenesis is still being explored

47
Q

What is prominent hypothesis of clusterin?

A

clusterin’s ability to bind Aβ peptides and thereby influence their aggregation, deposition and clearance, but the underlying mechanism(s) remain to be delineated.

48
Q

What does PICALM gene encode for?

A

Accessory protein in the endocytic pathway

49
Q

What is the function of PICALM?

A

regulates the formation of the clathrin lattice during endocytosis

50
Q

What has been associated with AD

A

• Multiple SNPs within and around the PICALM gene

51
Q

what does prominent hypothesis suggest about PICALM?

A

PICALM affects internalisation of APP (thus the production of Aβ) and endocytosis and trafficking of other molecules important for neuronal function

52
Q

What are the two ways of looking at role of PICALM?

A
  1. Directly interacting with APP

2. Interacting with other molecules involved in normal neuronal function

53
Q

Define Metabolome

A

complete set of metabolites found in a biological cell, tissue, organ or organism, representing the end products of cellular processes.

54
Q

Define Metabolomics

A

the systematic identification and quantification of small-molecule metabolite profiles of a biological system at a specific point in time

55
Q

What does metabolic profiling involve?

A

quantification of a specific group of metabolites for discrimination from different biological origins or status – with the goal of capturing the complexity of metabolic networks.

56
Q

What was LC-MS used to determine?

A

global metabolic changes in plasma and cerebrospinal fluid (CSF) from individuals with different Alzheimer’s disease severity.

57
Q

What is metabolome providing us with?

A

opportunities to see differences between ad patients and controls

58
Q

What can be affected in AD?

A

Cholesterol metabolism

markers xxx (11 decks)

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