Neurodegeneration

Question 1

What is the clinical diagnosis pathway for the different neurodegenerative disorders?

Answer 1

Question 2

What is prion disease?

Answer 2

A series of diseases with common molecular pathology​

Transmissible factor​

No DNA or RNA involved​

Prion (proteinaceous infectious only)

Question 3

What are the types of prion diseases?

Answer 3

Creutzfeldt-Jakob disease​

Gerstmann-Straüssler-Sheinker syndrome​

Kuru​

Fatal familial insomnia

Question 4

What changes may occur in prion disease?

Answer 4

Spongiform change

Prion protein deposits

Question 5

What is New Variant CJD?

Answer 5

Sporadic neuropsychiatric disorder​

Patients <45 yrs old​

Cerebellar ataxia​

Dementia​

Longer duration than CJD​

Linked to BSE​

Diagnosed at autopsy since 1990​

up to 14-10-21 178 deaths (none in last 5 yrs)

Question 6

What is the neuropathology of alzheimers disease?

Answer 6

Extracellular plaques​

Neurofibrillary tangles​

Cerebral amyloid angiopathy (CAA)​

Neuronal loss (cerebral atrophy)

Question 7

What does this imaging show?

Answer 7

Coritcol atrophy

Question 8

What is this?

Answer 8

Senile plaques

Question 9

What is this?

Answer 9

Cerebral amyloid angiopathy

Question 10

What is the structure of APP?

Answer 10

Question 11

What is APP processing?

Answer 11

Question 12

What is Abeta?

Answer 12

Abeta- disrupts intracellular processes like calcium dysfunction, synaptic dysfunction, proteasome function, mitochondrial function​

Abeta- hyperphosphorylated tau may be linked

Question 13

What is this?

Answer 13

Tau tangle on immunostaining

Question 14

Tau immunostaining in the peristriate but not the striate cortex is consistent with which Braak grading?​
II​

III​

IV​

V​

VI​

Answer 14

V

Question 15

What is Braak staging?

Answer 15

Staging system for Tau pathology in AD

Question 16

What is Aducanumab?

Answer 16

First drug that slows AD

Question 17

What is the neuropathology of PD?

Answer 17

Striatum Nigra dopaminergic neurone loss

Lewy Bodies

Question 18

What is the alpha synuclein pathology?

Answer 18

Polymeropoulos in 1997 found that mutations in the α-synuclein gene can result in PD​

Spillantini reported that Lewy bodies and Lewy neurites are immunoreactive for α-synuclein​

Now α-synuclein immunostaining is considered as the diagnostic gold standard

Question 19

What are the types of parkinsonism?

Answer 19

Idiopathic Parkinson’s disease​

Drug-induced Parkinsonism​

Multiple system atrophy​

Progressive supranuclear palsy​

Corticobasal degeneration​

Vascular pseudoparkinsonism ​

Alzheimer’s changes​

Fronto-temporal neurodegenerative disorders ​

20 other disorders

Question 20

Question 21

What is Pick’s disease?

Answer 21

Fronto-temporal atrophy​

Marked gliosis and neuronal loss​

Balloon neurons​

Tau positive Pick bodies

Question 22

Whats is the structure of Tau?

Answer 22

Single gene on 17q21​

16 exons​

Alternative splicing gives rise to 6 isoforms​

3R or 4R-tau (microtubule-binding domains)​

Two further inserts with unknown function​

Shortest form (3R/0N) foetal

Question 23

What are the Tau isoforms?

Answer 23

Question 24

Which proteins are associated with FTD?

Answer 24

FUS

progranulin gene

TDP

Question 25

What is the current classification of FTLDs?

Answer 25