Histopathology 16 - Neurodegeneration Flashcards
Recall 4 histopatological features of a brain with Alzheimer’s dementia
Extracellular plaques
Neurofibrillary tangles
Cerebral amyloid angiopathy
Neuronal loss (cerebral atrophy)
What does Tau staining show in Alzheimer’s disease?
Hyperphosphorylation
How is Alzheimer’s disease diagnosed at post-mortem?
Tau staining
What grading is used to stage Alzheimer’s disease at post-mortem?
Braak grading
Pathological changes begin in hippocampus and spread to occipital cortex - degree of spread guides staging
What is the basic pathophysiology of Parkinson’s disease?
Loss of dopaminergic cells in the substantia nigra, which project onto the striatum to control movement
What disease are “balloon neurons” associated with?
Frontotemporal dementia/ Pick’s disease
Which neurodegenerative disease shows 4R 3R tauopathy?
Alzheimer’s dementia
Which neurodegenerative disease shows 4R tauopathy?
Progressive supranuclear palsy
Which neurodegenerative disease shows 3R tauopathy?
Pick’s disease
Which neurodegenerative disease can be caused by a progranulin Z mutation?
Frontotemporal dementia (in this case there would be no tau pathology)
What abnormalities does dementia always have to involve?
Aphasia= language disorder (may be expressive or receptive)
• Apraxia= loss of ability to carry out learned purposeful tasks
• Agnosia= loss of ability to recognise object, people etc.
Which protein is misfolded in alzheimers?
Which is a better marker of disease?
Tau (intracellular)
Beta amyloid - senile plaques (extracellular)
**intracellular tau is a better marker of disease
Which protein is misfolded in DLB?
Alpha synuclein
Ubiquitin
Which protein is misfolded in corticobasal degeneration?
Tau
Which protein is misfolded in FTD linked to Chr 17?
Tau
Which protein is misfolded in pick’s disease?
Tau
Findings in AZ
generalised atrophy of the brain, widened sulci, narrowed gyri and enlarged ventricles (most marked in temporal and frontal lobes with loss of cholinergic neurons).
DLB
Psychological disturbances occur early. Day-to-day fluctuations in cognitive performance, visual hallucinations, spontaneous motor signs of Parkinsonism, recurrent falls and syncope, pathologically indistinguishable from PD
Pathophysiogy of parkinson’s disease
↓ stimulation of the motor cortex by the basal ganglia (caused by death of dopaminergic neurons in substantia nigra)
Features of PD
TRAP
tremor
rigidity
akinesia
postural instability
**with some psychiatric features eg PD dementia, hallucinations, anxiety
What protein is present in idiopathic parkinson’s disease?
Lewy bodies in affected neurones
these contain alpha synuclein
*α-synuclein immunostaining is considered DIAGNOSTIC GOLD STANDARD
What are the parkinson plus syndromes?
Lewy body dementia
progressive supranuclear palsy
corticobasal syndrome
multiple system atrophy
vascular parkinsonism
Which of the parkinson plus syndromes has alpha synuclein pathology?
Multiple system atrophy
*A for atrophy
a for alpha synuclein
Symptoms of DLB
– fluctuating cognition, visual hallucinations and early
dementia
Symptoms of PSP
tauopathy with limited vertical gaze (downgaze
more specific), early falls, axial rigidity and akinesia, dysarthia, and dysphagia
Sx of corticobasal syndrome
tauopathy with varied presentations but classically
presents with unilateral parkinsonism, dystonia/myoclonus, apraxia ± “alien limbs” phenomenon; may also present as progressive non-fluent aphasia
What is multiple system atrophy?
synucleinopathy presenting as either cerebellar
predominant (MSA-C, previously olivopontocerebellar atrophy) or parkinsonism predominant (MSA-P, previously nigrostriatal degeneration); both are associated with early autonomic dysfunction (previously Shy-Drager syndrome)
What isvascular parkinsonism?
multi-infarct presentation with gait instability and lower body
parkinsonism; less likely associated with tremor
Myelin Basic Protein and Proteo-lipid protein
multiple sclerosis
Which disorders have tau?
- Alzheimer’s disease: 3 dense bands, all 6 types of tau when dephosphorylated
- PSP: 2 dense bands, 4r when dephosphorylated
- CBD: 2 dense bands, 4r when dephosphorylated
- Pick’s disease: 3r tauopathy
**mb not all of these cause dementia - only AD, pick’s disease
PSP and CBD are the parkinson plus syndromes
