Neurodegeneration Flashcards
What is the neuropathology of AD?
Extracellular plaques: accumulation of protein in brain parenchyma
Neurofibrillary tangles: disruption of neuronal cytoskeleton
Cerebral amyloid angiopathy (CAA)
Neuronal loss (cerebral atrophy)
What can be seen here? What are these?
Senile plaques: lumps of protein in brain
Tangles
What is this? Where else can this protein be found?
Cerebral amyloid angiopathy
Can be found in blood vessel walls in varying extents in different cases
What can be seen here?
Tau immunostaining
Cytoskeleton protein, abnormal Tau is stained brown by antibody
Which drug for Alzheimer’s has not yet been approved?
Aducanumab
What is this?
Locus classicus
Low pigmented substantia nigra in Parkinson’s
Due to loss of dopaminergic neurones which contain neuromelanin pigment
What is this?
Lewy Body
What is this?
Lewy Body
What is this?
Lewy Body
What is the pathology of α-synuclein?
Mutations in α-synuclein gene can result in PD.
Lewy bodies + Lewy neurites are immunoreactive for α-synuclein.
α-synuclein immunostaining is diagnostic gold standard.
What are these?
α-synuclein immunostaining
What are these? What does this illustrate?
α-Syn deposits in epicardial nerve fascicles (e, f)
Paravertebral sympathetic ganglia (a, b).
Pathology not restricted to CNS- peripheral autonomic ganglia
Also found in the nose
What are 7 causes of Parkinsonism?
Idiopathic
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 this? How does this present? Describe the pathology
Multiple System Atrophy (MSA)
A/W falls, can mimic parkinsons
Alpha synucleinopathy: accumulates more in glial support cells rather than neurones
(same protein, different cellular substrate)
What is this? What is the pathology?
Corticobasal Degeneration (CBD)
Astrocytic tau plaques
(NOT alpha synucleinopathy)
What is this? What problems sometimes characterise this? What is the pathology?
Progressive supranuclear palsy (PSP)
Vertical eye movement problems
Tau-opathy
(NOT alpha synucleinopathy)
What is this?
Progressive supranuclear palsy (PSP)
What are features of Pick’s Disease?
Fronto-temporal atrophy
Marked gliosis and neuronal loss
Balloon neurons
Tau positive Pick bodies
What is this?
Tau positive Pick bodies
What is the structure of the TAU protein?
Single gene on 17q21
16 exons
Alternative splicing gives rise to 6 isoforms
3R or 4R-tau (microtubule-binding domains)
2 further inserts with unknown function
Shortest form (3R/0N) foetal
How are Prion diseases transmitted?
Transmissible factor: transmission of protein causes disease in recipient
No DNA or RNA involved
PRoteinaceous Infections ONly
Name 4 prion diseases seen in humans
Creutzfeldt-Jakob disease
Gerstmann-Straüssler-Sheinker syndrome
Kuru
Fatal familial insomnia
Describe prion diseases
Proteinopathies
Prion protein deposits
Spongiform change: holes appear in tissue
Host protein structure is changed by infected protein- causes pathology
Describe the aetiology and epidemiology of new variant CJD. Give 2 symptoms of vCJD
Sporadic neuropsychiatric disorder
Linked to BSE: ingestion of infected bovine material
Longer duration than CJD
<45y
Cerebellar ataxia
Dementia
What features are present in the right hand image suggestive of Alzheimer’s disease?
Cortical atrophy
Thinning of cortex
Widening of sulci
Thinning of gyri
Enlargement of ventricles
How do plaques form in Alzheimers disease?
Cleavage of amyloid precursor protein
Beta amyloid produced
Accumulation of beta amyloid intracellularly
Expelled beta amyloid forms plaques
What are the likely contributors to cell death in Alzheimers disease?
Interruption of cellular processes involved in:
Calcium homeostasis
Mitochondria + reactive oxygen species
Proteosome blockage
Intracellular tangle formation
What is used for the staging of Tau pathology? What is diagnosis based on?
Braak staging
Dx based on amount + site in brain
Nearly all >60s will show some signs of Alzheimers in the brain though not symptomatic
Describe the spread of Tau pathology in Alzheimers disease
- Around hippocampus
- Posterior hippocampus
- Temporal cortex
- Occipital cortex
Where do the neurones in the substantial nigra project to?
Neurones project to striatum in basal ganglia where initiation of movement is controlled
What are Lewy bodies?
Eosinophilic inclusions in pigmented neurones
Composed of aggregates of the protein alpha synuclein
