Lecture 19: Frontotemporal Dementia

Question 1

What is FTD?

Answer 1

Frontotemporal dementia: a group of disorders that cause progressive nerve cell loss in the frontal and temporal lobes of the brain.

Question 2

What is the age range of individual diagnosed with FTD?

Answer 2

45-65 years
-most common in younger people
-50,000 - 60,000 people with FTD in US

Question 3

Which are the types of FTD?

Answer 3

-behavior variant FTD
-primary progressive aphasia (PPA)
—-> semantic variant PPA
—-> non-fluent variant PPA

Question 4

What are the characteristics of behavior variant FTD?

Answer 4

bvFTA: changes in personality including apathy, socially inappropriate activities, loss of empathy, poor decision making and judgement.
EX: Phineas Gage had an accident but became aggressive so he was the first look at how damage to the frontal lobe affects a person.

Question 5

What are the characteristics of PPA?

Answer 5

problems with speaking, writing or comprehension this is due to the degeneration of the temporal lobe.

Question 6

What are the characteristics of svPPA?

Answer 6

trouble understanding the meaning of words, finding words or naming people and objects.

Question 7

What are the characteristics of nfvPPA?

Answer 7

difficulty producing speech and/or omitting words, using incorrect tenses or word endings.
-People affected tend to speak like children often.

Question 8

What two proteins are the primary cause of FTD?

Answer 8

Tau and TDP-43 are associated with the cause of FTD due to abnormal accumulation in the brain

Question 9

FTD cases are familial. Which genes are affected by these mutations?

Answer 9

-C9orf72
-Progranulin (GRN)
-Tau (MAPT)

Question 10

Many genes implicated in FTD are also involved in which other disease?

Answer 10

ALS

Question 11

Progranulin (GRN) is predominately expressed by __

Answer 11

microglia

Question 12

Tau (MAPT) is expressed by _

Answer 12

neurons

Question 13

What kind of protein is progranulin ?

Answer 13

lysosomal protein

Question 14

What do reduced GRN levels cause?

Answer 14

-homozygous GRN mutations in lysosomal storage disease
-heterozygous GRN mutations in FTLD
-GRN SNP associated to neuro degeneration

Question 15

What do increased GRN levels cause ?

Answer 15

-bio marker for cancer invasion and metastasis
-bio marker for metabolic disease
-bio marker for neuro inflammation
-bio marker for disease activity in auto immune disease

Question 16

Approximately 5-10% of all FTD patients carry this kind of mutation

Answer 16

Heterozygous loss of function GRN mutations

Question 17

What occurs to mutant GRN transcripts?

Answer 17

they undergo a nonsense mediated decay which reduces the overall amount of GRN protein