Fronto-Temporal Dementias

Question 1

Key clinical features of FTDs?

Answer 1

• semantic dementia
• behavioural variant
• progressive non-fluent aphasia

Question 2

Neuropathological features of Pick’s Disease?

Answer 2

• Frontal symptoms
• sporadic tauopathy (no MAPT mutation)
• F-T atrophy (“knife edge atrophy”)
• tau positive PIck bodies
• marked gliosis and neuronal loss
• balloon neurons

Question 3

No. of isoforms of tau protein?

Answer 3

6 isoforms

Question 4

Isoforms of tau antibodies?

Answer 4

PHF1 antibody ]- general
4R-Tau antibody
3R-Tau antibody]- Pick’s bodies

Question 5

Clinical correlate of 3R/4R tauopathy?

Answer 5

AD

and
FTLD w/ 3R and 4R Tau (V337M, R406W)

Question 6

Clinical correlate of 4R tauopathy?

Answer 6

CBD
PSP

and
FLTLD w/ 4R Tau (P301L)

Question 7

Clinical correlate of 3R tauopathy?

Answer 7

Pick’s Disease

and
FTLD w/ 3R Tau (K257T, G389R)

Question 8

Spectrum of Tau FTD pathology (+neuropath features): Pick’s, CBD and PSP?

Answer 8

Pick’s Disease: Pick bodies

CBD: astrocytic plaques

PSP: coiled bodies, tufted astrocytes

Question 9

On what chromosome is the tau gene located

Answer 9

Chr 17

Question 10

Tau -ve, TDP+ve, ubiquitin +ve, neuronal inclusions in FTD?

Answer 10

Progranulin (function currently unknown)

Mutated progranulin (adjacent to MAPT Tau gene)

-> instracytoplasmic and intranuclear inclusions

Question 11

Molecular subtypes of FTD?

Answer 11

• Tauopathies: 3R/4R, 4R, 3R
• Progranulin
• TDP-43
• FUS
• C9orf72`

Question 12

MRI imaging changes in FTDs?

Answer 12

Assymetrical atrophy

Question 13

TDP-43 subtypes?

Answer 13

A- semantic dementia
B- C9orf72
C- progranulin, FTD
D

Question 14

What is FUS regading FTD?

Answer 14

“Fused in Sarcoma”

Characteristic inclusion accounting for some atypical FTD

Ubiquitin +ve

Question 15

What is C9orf72 regarding FTD?

Answer 15

Commonly associated w/ ALS

Ubiquitin +ve
TDP-43 +ve
C9orf72 +ve inclusion in cerebellum (other parts TDP43 -ve)

Question 16

Current classification of FTLD

Answer 16

Tau +ve FTLD
3R tauopathy
4R tauopathy
3R/4R tauopathy

Tau -ve FTLD
TDP-43 +ve, ubiquitin +ve]- FTLD-TDP (type A-D)
TDP-43 -ve, ubiquitin +ve (FTLD-FUS, FTLD-UPS)
TDP-43 -ve, ubiquitin -ve (DLDH)

Question 17

What is DLDH?

Answer 17

Dementia lacking distinctive histology

Question 18

What mutation causes FTLD-UPS?

Answer 18

Mutation in CHMP2B gene

Question 19

Tauopathies and FTLD generally?

Answer 19

Many tauopathies are grouped under the term FTLD (even if they are not strictly FTLD)