Histopathology 16 - Neurodegeneration

Question 1

Recall 4 histopatological features of a brain with Alzheimer’s dementia

Answer 1

Extracellular plaques
Neurofibrillary tangles
Cerebral amyloid angiopathy
Neuronal loss (cerebral atrophy)

Question 2

What does Tau staining show in Alzheimer’s disease?

Answer 2

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

Question 3

How is Alzheimer’s disease diagnosed at post-mortem?

Answer 3

Tau staining

Question 4

What grading is used to stage Alzheimer’s disease at post-mortem?

Answer 4

Braak grading

Pathological changes begin in hippocampus and spread to occipital cortex - degree of spread guides staging

Question 5

What is the basic pathophysiology of Parkinson’s disease?

Answer 5

• 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

Question 6

What is the role of Lewy bodies in Parkinson’s disease?

Answer 6

Cause a mutation in alpha synuclein

Question 7

What disease are “ballroom neurons” associated with?

Answer 7

Frontotemporal dementia/ Pick’s disease

Question 8

Which neurodegenerative disease shows 4R 3R tauopathy?

Answer 8

Alzheimer’s dementia

Question 9

Which neurodegenerative disease shows 4R tauopathy?

Answer 9

Progressive supranuclear palsy

Question 10

Which neurodegenerative disease shows 3R tauopathy?

Answer 10

Pick’s disease

Question 11

Which neurodegenerative disease can be caused by a progranulin Z mutation?

Answer 11

Frontotemporal dementia (in this case there would be no tau pathology)

Question 12

Aetiology of prion disease

Answer 12

• 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

Question 13

spongiform encephalopathies on histology - which neuro condition?

Answer 13

Prion diseases

Question 14

Which part of the brain are plaques formed by prion protein?

Answer 14

cerebellum

Question 15

neurofibrillary tangles and extracellular plaques seen in which neuro condition?

Answer 15

Alzheimer’s

Question 16

Pathophysiology of Alzheimer’s

Answer 16

• massively enlarged ventricles
• Cortical atrophy
• THINNING of the cortex and gyri
• widening of the sulci

Question 17

Name of extracellular plaques seen in Alzheimer’s

Answer 17

amyloid-beta

Question 18

6 Braak stages

Answer 18

• 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)

Question 19

What molecule is present in Parkinson’s, and what is it made of?

Answer 19

Lewy bodies - intracellular accumulations of a-synuclein

Question 20

Diagnostic gold standard for Parkinson’s

Answer 20

a-synuclein immunostaining

Question 21

Excluding Parkinson’s disease, which other disorder often presenting with Parkinsonism, is associated with a-synuclein pathology?

Answer 21

Multiple System Atrophy (MSA)

Question 22

3 histological findings in Pick’s disease (frontotemporal dementia)

Answer 22

• Marked gliosis and neuronal loss
• Balloon neurons
• Tau-positive Pick bodies (get mutations in Tau)