Neurodegeneration Flashcards
What is the clinical diagnosis pathway for the different neurodegenerative disorders?
What is prion disease?
A series of diseases with common molecular pathology
Transmissible factor
No DNA or RNA involved
Prion (proteinaceous infectious only)
What are the types of prion diseases?
Creutzfeldt-Jakob disease
Gerstmann-Straüssler-Sheinker syndrome
Kuru
Fatal familial insomnia
What changes may occur in prion disease?
Spongiform change
Prion protein deposits
What is New Variant CJD?
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)
What is the neuropathology of alzheimers disease?
Extracellular plaques
Neurofibrillary tangles
Cerebral amyloid angiopathy (CAA)
Neuronal loss (cerebral atrophy)
What does this imaging show?
Coritcol atrophy
What is this?
Senile plaques
What is this?
Cerebral amyloid angiopathy
What is the structure of APP?
What is APP processing?
What is Abeta?
Abeta- disrupts intracellular processes like calcium dysfunction, synaptic dysfunction, proteasome function, mitochondrial function
Abeta- hyperphosphorylated tau may be linked
What is this?
Tau tangle on immunostaining
Tau immunostaining in the peristriate but not the striate cortex is consistent with which Braak grading?
II
III
IV
V
VI
V
What is Braak staging?
Staging system for Tau pathology in AD
What is Aducanumab?
First drug that slows AD
What is the neuropathology of PD?
Striatum Nigra dopaminergic neurone loss
Lewy Bodies
What is the alpha synuclein pathology?
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
What are the types of parkinsonism?
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
What is Pick’s disease?
Fronto-temporal atrophy
Marked gliosis and neuronal loss
Balloon neurons
Tau positive Pick bodies
Whats is the structure of Tau?
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
What are the Tau isoforms?
Which proteins are associated with FTD?
FUS
progranulin gene
TDP
What is the current classification of FTLDs?
