Histopathology 20: Neurodegeneration Flashcards
What are prion diseases ?
Prions are proteinaceous infections particles. They can cause Prion protein (PrP) to miss fold and become soluble.
This can cause neurodegenerative diseases in humans.
What is the main sign of prion disease ?
Rapid neurodegenerative decline
List 4 Prion types of prion diseases seen in humans ?
CJD- Creutzfeldt-Jakob disease
GSSS- gerstmann-straussler-sheinker syndrome
Kuru
Fatal familial insomnia
List 2 common features of prion diseases on histology ?
Spongiform change
Prion protein deposition
Describe the progression in symptoms of Alzheimer’s disease ?
recent memory loss (cognitive) -> dressing apraxia (parietal lobe) -> executive function problems, personality changes, disinhibition (frontal lobe)
List the classical pathological features of Alzheimer’s disease ?
Extracellular plaques
Neurofibrillary tangles
Cerebral amyloid angiopathy
Neuronal loss (cerebral atrophy)
What is the protein responsible for plaque formation in Alzheimer’s disease ?
Amyloid-beta
How is the Amyloid-beta protein formed ?
APP (amyloid precursor protein) is cleaved by enzymes in the cell membrane.
Why is Tau protein a useful marker in neuropathology (Braak staging) ?
It spreads throughout the brain and the parts it affects is closely related to the symptoms seen in the patient.
What disease with tauopathy is commonly seen in boxers ?
Chronic Traumatic Encephalopathy
Occurs after multiple repetitive traumatic head injuries
The presence of ………. characterises Parkinson’s disease
Lewy bodies
Death of……… cells from the ………….up to the basal ganglia causes Parkinson’s disease
Dopaminergic
Substantial nigra
What are Lewy bodies ?
Accumulation of the protein Alpha-synuclein.
Seen as Smooth hyaline inclusions in the pigmented cells of the substantia nigra.
What is the gold standard test for Parkinson’s disease ?
Alpha-synuclein immunostaining
Where in the brain does Alzheimer’s disease originate ?
The temporal lobe (hippocampus)
Where does Parkinson’s disease originate in the CNS ?
The medulla
List 3 of the main differentials that cause Parkinsonism (Parkinson like symptoms)
MSA - multisystem atrophy
CBD - corticobasal degeneration
PSP - progressive supranuclear palsay
What is considered to be prodromal for Parkinson’s disease ?
Sleep disorders
Where do you get alpha-synuclein deposition in MSA disease ?
Glial cells
Which disease is characterised by Pick Bodies and balloon neurons ?
Pick’s disease
What symptoms does Pick’s disease cause ?
Dysexecutive syndrome
Aggression
Disinhibition
(Frontal lobe)
What are Pick bodies ?
Tau deposits
List 4 areas of cognitive disturbance affected in Dementia ?
Amnesia: Memory loss
Aphasia: Language disorder
Apraxia: Unable to carry out purposeful tasks
Agnosia: Unable to identify objects/ faces
Which parkinson plus syndrome presents with the characteristic feature of “Alien limbs”?
Corticobasal syndrome (CBD)
Which cells produce myelin ?
oligodendrocytes
List features of Multiple Sclerosis ?
- Optic neuritis
- Parasthesia
- Weakness
- Loss of coordination
- Incontinence
- Depression
Lumbar puncture with CSF sample showing myelin basic protein and proteo-lipid protein.
Most likely diagnosis ?
MS
pathophysiology of prion disease
normal prion protein can unfold and refold into a beta-pleated sheet
this is more susceptible to aggregation
once some of this forms, it can propagate
leads to insoluble protein accumulating in the parenchyma of the brain
features of new variant CJD (vCJD)
sporadic neuropsychiatric disorder
<45yrs
cerebellar ataxia + dementia
linked to BSE
neuropathology of Alzheimers
- EC plaques (amyloid-beta)
- neurofibrillary tangles
- cerebral amyloid angiopathy (CAA)
- neuronal loss (cerebral atrophy)
where is a-beta most toxic
intra-celularly
A-beta oligomers and protofibrils interfere with normal cell functions
how does tau protein result in Alzheimers
maintains stability of the cytoskeleton
becomes hyperphosphorylated
accumulates inside the cell and causes cell death
Braak stags based on the location of tau pathology
features of PD
presence of lewy bodies
neuromelanin produced by dopaminergic cells in the substantial nigra give it its colour
PD - death of dopaminergic cells of the SN - loss of colour
SN links to BG - important in the initiation of movement
pill-rolling tremor and akinesia
Lewy bodies = IC accumulations of alpha-synuclein
what are Braak stages used in PD
based on distribution of alpha-synuclein pathology
originates in the brainstem
anosmia = early sig
sleep disorders = prodrome
what conditions can cause parkinsonism
idiopathic PD drug-induced parkinsonism multiple system atrophy PSP corticobasal degeneration
*3 main DD =
MSA, CBD, PSP
what is pick’s disease
fronto-temporal atrophy presents with frontal lobe pathology eg dysexecutive syndrome gliosis and neuronal loss balloon neurons tau-positive pick bodies
difference between AD and CBD+ PSP on western blot of tau
AD - forms 3 bands
CBD+ PSP - 2 dense bands
Pick’s disease - 3R tauopathy
features of fronto-temporal dementia
mutations in tau and progranulin
problems with TDP-43 (trafficking protein) = basis of some types of FTD
