Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

NEUR0010 > Frontotemporal Dementia > Flashcards

Frontotemporal Dementia Flashcards

1
Q

Name the 3 types of FTD

A

Behavioural variant FTD
Progressive non-fluent aphasia
Semantic dementia

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

What are the main symptomatic differences between FTD and AD?

A

Episodic memory, navigation, general intellect preserved

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

What are the symptoms of behavioural variant FTD?

A 
Decline in interpersonal and executive skills
Lack of empathy
Abnormal behaviours (e.g. obsessions, stereotypies)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the symptoms of progressive non-fluent aphasia?

A

Effortful non-fluent speech

Apraxia of other orofacial movements

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

What are the symptoms of semantic dementia?

A

Decline of semantic memory

Initially affects knowledge of word meanings

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

How can CSF protein markers be used to molecularly distinguish AD from FTD?

A

In AD increased ratio of tau:AB42

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

What is the pathological name for FTD?

A

Frontotemporal lobar degeneration (FTLD)

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

What are the 3 macroscopic features of FTD brains?

A

Frontal and temporal lobe atrophy
Enlarged lateral ventricles
Hippocampal atrophy

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

What is the effect of hippocampal atrophy?

A

Spatial navigation difficulties - later in disease

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

Name the 4 molecular subtypes of FTLD and their relative rarities

A

FTLD-TDP - most common
FTLD-tau - common
FTLD-FET - rare
FTLD-UPS - very rare

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

What is the physiological role of tau and why is this important?

A

Promotes microtubule stability

Key for neuronal integrity and axonal transport

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

Which gene encodes tau?

A

MAPT

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

How many tau isoforms can be formed by alternative splicing?

A

6

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

What are the microscopic features of FTLD-tau?

A

Pick bodies in temporal lobe

Tufted astrocytes - tau deposition within

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

What is the physiological role of TDP-43 and why is this important?

A

Binds multiple RNAs

Key for RNA processing

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

What is the main microscopic feature of most FTLD-TDP cases?

A

Cytoplasmic inclusion bodies - TDP43+, ubiquitin+, tau-

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

Where is TDP-43 normally localised to?

A

Nucleus

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

Which abnormal modifications are found on pathological TDP-43?

A

Hyperphosphorylation
Ubiquitination
N-terminal truncation

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

How do the 4 FTLD-TDP subtypes vary?

A

Different inclusion morphology

Different inclusion cortical layer distribution

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

What is the physiological role of FET and why is this important?

A

Binds RNA/DNA

Key for DNA and RNA processing

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

Which markers label inclusions in FTLD-UPS and what does this suggest?

A

UPS markers

Problem with protein degradation systems

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

Mutations in which gene cause FTLD-UPS?

A

CHMP2B

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

What are the inclusions in FTLD-UPS composed of?

A

Ubiquitin

p62

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

Which gene is linked to both ALS and FTD?

A

C9orf72

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Which mutation type in C9orf72 causes FTD and ALS?
Hexanucleotide repeat expansions
26
Give the main component of inclusions in ALS and their frequency
TDP-43 - 97% | SOD-1 - 2%
27
Give the main component of inclusions in FTD and their frequency
Tau - 45% TDP-43 - 45% FUS - 9%
28
Name 3 major autosomal dominant causes of FTD
MAPT GRN C9orf72
29
What is seen in neurons from MAPT mutant FTD patient-derived iPSCs and what does this suggest?
Endosome accumulation, decreased lysosomes | Impaired endocytic trafficking
30
Where is GRN expressed?
Mature neurons | Microglia
31
What does GRN encode?
Progranulin
32
What is the disease mechanism of FTD due to a GRN mutation?
GRN haploinsufficiency - loss-of-function
33
What is the effect of an absence of progranulin in neurons?
Decreased neurite outgrowth
34
Which condition does a homozygous-null GRN mutation result in and what does this involve?
Neuronal ceroid lipofuscinosis (NCL) | Storage of abnormal lipopigment in lysosomes
35
What is the sequence of a hexanucleotide repeat in C9orf72?
GGGGCC
36
Are the hexanuclotide repeats in C9orf72 intronic or exonic?
Intronic
37
How many hexanucleotide repeats are usually in C9orf72?
2-24
38
How many hexanucleotide repeats are in C9orf72 in FTD-ALS?
100s/1000s
39
What are the 3 possible disease mechanisms for C9orf72 in FTD/ALS?
Decreased C9orf72 levels Bidirectional transcription of repeats - forms sense and antisense RNA foci - sequester RNA-binding proteins Dipeptide repeat proteins (DPRs) - toxic - from sense and antisense RNA RAN translation
40
What the physiological role of C9orf72?
Associated with autophagosomes - role in autophagy
41
Where do the C9orf72 repeat RNA foci form?
Nucleus | Cytoplasm
42
How do C9orf72 repeat RNAs sequester RNA-binding proteins?
G bases in repeat RNAs bind - via atypical pairing Form square planar structures Stack - form G-quadruplex Traps RNA-binding proteins
43
Where are C9orf72 dipeptide repeat proteins (DPRs) found?
Cytoplasm | Nucleus
44
How does RAN translation differ from normal translation?
Non-canonical - no AUG start codon
45
How many dipeptide repeat proteins (DPRs) are generated from C9orf72 hexanucleotide expanded repeats?
5
46
What enables the formation of so many dipeptide repeat proteins (DPRs) from the C9orf72 hexanucleotide repeat expansion?
Bidirectional transcription - sense and antisense mRNA | Translation in 3 reading frames
47
Name 3 minor genetic FTD causes
CHMP2B VCP TARDBP
48
What is the physiological role of CHMP2B?
Part of endosomal sorting complex | Sorts proteins to late endosome and lysosome - for degradation
49
Where in CHMP2B does the FTD-causing mutation occur and how does affect the protein?
In splice site | C-terminal truncation
50
What can be seen in the neurons of FTD patients caused by CHMP2B mutation and what does this suggest?
Abnormally high lipoprotein deposition in neurons | Suggests lysosomal storage pathology
51
Which diseases does VCP mutation cause?
FTD and inclusion body myopathy - IBMFTD
52
What is the inheritance pattern of IBMFTD?
Autosomal dominant
53
What is the physiological role of VCP?
Protein homeostasis
54
What does TARDBP encode?
TDP-43
55
Name a gene with an FTD risk variant
TMEM106B
56
What is the effect of the TMEM106B FTD risk variant?
Increases TMEM106B levels
57
What is the physiological role of TMEM106B?
Lysosome size, acidification, function, transport
58
What are the advantages of Drosophila as neurodegenerative disease models?
``` Cheap Short lifespan Complex behaviour - e.g. learning, memory Fewer genes than humans Widely-available molecular genetic tools ```
59
What are the disadvantages of Drosophila as neurodegenerative disease models?
Not as complex as humans - may lack relevant pathology | Lack some genes
60
What are the advantages of cell lines as neurodegenerative disease models?
Immortal Cheap No ethical issues
61
What are the disadvantages of cell lines as neurodegenerative disease models?
Not neuronal | Altered morphology to tissue origin
62
What are the advantages of mice as neurodegenerative disease models?
Genetically malleable | Fairly short lifespan
63
What are the disadvantages of mice as neurodegenerative disease models?
Lack complex neuron circuits Lack full complement of glia Lack vascular and immunologic components
64
What are the advantages of iPSCs as neurodegenerative disease models?
Contain mutation from patient derived from Can be differentiated into multiple cell types No ethical issues
65
What are the disadvantages of iPSCs as neurodegenerative disease models?
In dish - lack supporting glia | Demanding - require daily attention

NEUR0010 (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions