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
NB so if Tau protein is important for maintaining the stability of the cytoskeleton - so if it becomes hyperphosphorylated, it starts causing problems as this interferes with its normal function - causes cell death
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?
- death of the dopaminergic cells of the substantia nigra so the coloration of the substantia nigra is LOST
- Dopaminergic cells from the substantia nigra project to the basal ganglia
- The basal ganglia is very important in the initiation of movement
What is the role of Lewy bodies in Parkinson’s disease?
Cause a mutation in alpha synuclein
What disease are “ballroom 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)
Aetiology of prion disease
- purely a protein-protein interaction
- There is a transmissible factor
- NO DNA or RNA transfer involved in the transmission
- Prion (proteinaceous infectious only)
- Includes Creutzfeldt-Jakob disease, Gerstmann-Straussler-Sheinker (GSS) syndrome
spongiform encephalopathies on histology - which neuro condition?
Prion diseases
Which part of the brain are plaques formed by prion protein?
cerebellum
neurofibrillary tangles and extracellular plaques seen in which neuro condition?
Alzheimer’s
Pathophysiology of Alzheimer’s
- massively enlarged ventricles
- Cortical atrophy
- THINNING of the cortex and gyri
- widening of the sulci
Name of extracellular plaques seen in Alzheimer’s
amyloid-beta
6 Braak stages
- Stage I- Tau pathology is found in the temporal lobe, in the anterior hippocampus (entorhinal region) and spreads throughout the whole entorhinal cortex
- Stage II- Spreads back to the posterior hippocampus and out towards the temporal cortex
- By Stage III- you can see the immunostaining by eye, affects the substantia nigra
- Stage IV- it spreads out of the temporal lobe and into the superior temporal gyrus
- Stage V- it spreads to the peristriate cortex (cortex around the primary visual cortex)
- Stage VI- spread to the striate cortex (occipital lobe)
What molecule is present in Parkinson’s, and what is it made of?
Lewy bodies - intracellular accumulations of a-synuclein
Diagnostic gold standard for Parkinson’s
a-synuclein immunostaining
Excluding Parkinson’s disease, which other disorder often presenting with Parkinsonism, is associated with a-synuclein pathology?
Multiple System Atrophy (MSA)
3 histological findings in Pick’s disease (frontotemporal dementia)
- Marked gliosis and neuronal loss
- Balloon neurons
- Tau-positive Pick bodies (get mutations in Tau)
