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

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

Loss of dopaminergic cells in the substantia nigra, which project onto the striatum to control movement

Question 6

What disease are “balloon neurons” associated with?

Answer 6

Frontotemporal dementia/ Pick’s disease

Question 7

Which neurodegenerative disease shows 4R 3R tauopathy?

Answer 7

Alzheimer’s dementia

Question 8

Which neurodegenerative disease shows 4R tauopathy?

Answer 8

Progressive supranuclear palsy

Question 9

Which neurodegenerative disease shows 3R tauopathy?

Answer 9

Pick’s disease

Question 10

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

Answer 10

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

Question 11

What abnormalities does dementia always have to involve?

Answer 11

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.

Question 12

Which protein is misfolded in alzheimers?

Which is a better marker of disease?

Answer 12

Tau (intracellular)

Beta amyloid - senile plaques (extracellular)

**intracellular tau is a better marker of disease

Question 13

Which protein is misfolded in DLB?

Answer 13

Alpha synuclein

Ubiquitin

Question 14

Which protein is misfolded in corticobasal degeneration?

Answer 14

Tau

Question 15

Which protein is misfolded in FTD linked to Chr 17?

Answer 15

Tau

Question 16

Which protein is misfolded in pick’s disease?

Answer 16

Tau

Question 18

Findings in AZ

Answer 18

generalised atrophy of the brain, widened sulci, narrowed gyri and enlarged ventricles (most marked in temporal and frontal lobes with loss of cholinergic neurons).

Question 19

DLB

Answer 19

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

Question 20

Pathophysiogy of parkinson’s disease

Answer 20

↓ stimulation of the motor cortex by the basal ganglia (caused by death of dopaminergic neurons in substantia nigra)

Question 21

Features of PD

Answer 21

TRAP

tremor

rigidity

akinesia

postural instability

**with some psychiatric features eg PD dementia, hallucinations, anxiety

Question 22

What protein is present in idiopathic parkinson’s disease?

Answer 22

Lewy bodies in affected neurones

these contain alpha synuclein

*α-synuclein immunostaining is considered DIAGNOSTIC GOLD STANDARD

Question 23

What are the parkinson plus syndromes?

Answer 23

Lewy body dementia

progressive supranuclear palsy

corticobasal syndrome

multiple system atrophy

vascular parkinsonism

Question 26

Which of the parkinson plus syndromes has alpha synuclein pathology?

Answer 26

Multiple system atrophy \*A for atrophy a for alpha synuclein

Question 27

Symptoms of DLB

Answer 27

– fluctuating cognition, visual hallucinations and early dementia

Question 28

Symptoms of PSP

Answer 28

tauopathy with limited vertical gaze (downgaze more specific), early falls, axial rigidity and akinesia, dysarthia, and dysphagia

Question 29

Sx of corticobasal syndrome

Answer 29

tauopathy with varied presentations but classically presents with unilateral parkinsonism, dystonia/myoclonus, apraxia ± “alien limbs” phenomenon; may also present as progressive non-fluent aphasia

Question 30

What is multiple system atrophy?

Answer 30

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)

Question 31

What isvascular parkinsonism?

Answer 31

multi-infarct presentation with gait instability and lower body parkinsonism; less likely associated with tremor

Question 32

Myelin Basic Protein and Proteo-lipid protein

Answer 32

multiple sclerosis

Question 34

Which disorders have tau?

Answer 34

1. Alzheimer's disease: 3 dense bands, all 6 types of tau when dephosphorylated 2. PSP: 2 dense bands, 4r when dephosphorylated 3. CBD: 2 dense bands, 4r when dephosphorylated 4. 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