Histopathology 20: Neurodegeneration

Question 1

What are prion diseases ?

Answer 1

Prions are proteinaceous infections particles. They can cause Prion protein (PrP) to miss fold and become soluble.
This can cause neurodegenerative diseases in humans.

Question 2

What is the main sign of prion disease ?

Answer 2

Rapid neurodegenerative decline

Question 3

List 4 Prion types of prion diseases seen in humans ?

Answer 3

CJD- Creutzfeldt-Jakob disease
GSSS- gerstmann-straussler-sheinker syndrome
Kuru
Fatal familial insomnia

Question 4

List 2 common features of prion diseases on histology ?

Answer 4

Spongiform change

Prion protein deposition

Question 5

Describe the progression in symptoms of Alzheimer’s disease ?

Answer 5

recent memory loss (cognitive) -> dressing apraxia (parietal lobe) -> executive function problems, personality changes, disinhibition (frontal lobe)

Question 6

List the classical pathological features of Alzheimer’s disease ?

Answer 6

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

Question 7

What is the protein responsible for plaque formation in Alzheimer’s disease ?

Answer 7

Amyloid-beta

Question 8

How is the Amyloid-beta protein formed ?

Answer 8

APP (amyloid precursor protein) is cleaved by enzymes in the cell membrane.

Question 9

Why is Tau protein a useful marker in neuropathology (Braak staging) ?

Answer 9

It spreads throughout the brain and the parts it affects is closely related to the symptoms seen in the patient.

Question 10

What disease with tauopathy is commonly seen in boxers ?

Answer 10

Chronic Traumatic Encephalopathy

Occurs after multiple repetitive traumatic head injuries

Question 11

The presence of ………. characterises Parkinson’s disease

Answer 11

Lewy bodies

Question 12

Death of……… cells from the ………….up to the basal ganglia causes Parkinson’s disease

Answer 12

Dopaminergic

Substantial nigra

Question 13

What are Lewy bodies ?

Answer 13

Accumulation of the protein Alpha-synuclein.

Seen as Smooth hyaline inclusions in the pigmented cells of the substantia nigra.

Question 14

What is the gold standard test for Parkinson’s disease ?

Answer 14

Alpha-synuclein immunostaining

Question 15

Where in the brain does Alzheimer’s disease originate ?

Answer 15

The temporal lobe (hippocampus)

Question 16

Where does Parkinson’s disease originate in the CNS ?

Answer 16

The medulla

Question 17

List 3 of the main differentials that cause Parkinsonism (Parkinson like symptoms)

Answer 17

MSA - multisystem atrophy
CBD - corticobasal degeneration
PSP - progressive supranuclear palsay

Question 18

What is considered to be prodromal for Parkinson’s disease ?

Answer 18

Sleep disorders

Question 19

Where do you get alpha-synuclein deposition in MSA disease ?

Answer 19

Glial cells

Question 20

Which disease is characterised by Pick Bodies and balloon neurons ?

Answer 20

Pick’s disease

Question 21

What symptoms does Pick’s disease cause ?

Answer 21

Dysexecutive syndrome
Aggression
Disinhibition

(Frontal lobe)

Question 22

What are Pick bodies ?

Answer 22

Tau deposits

Question 23

List 4 areas of cognitive disturbance affected in Dementia ?

Answer 23

Amnesia: Memory loss
Aphasia: Language disorder
Apraxia: Unable to carry out purposeful tasks
Agnosia: Unable to identify objects/ faces

Question 24

Which parkinson plus syndrome presents with the characteristic feature of “Alien limbs” ?

Answer 24

Corticobasal syndrome (CBD)

Question 25

Which cells produce myelin ?

Answer 25

oligodendrocytes

Question 26

List features of Multiple Sclerosis ?

Answer 26

• Optic neuritis
• Parasthesia
• Weakness
• Loss of coordination
• Incontinence
• Depression

Question 27

Lumbar puncture with CSF sample showing myelin basic protein and proteo-lipid protein.

Most likely diagnosis ?

Answer 27

MS

Question 28

pathophysiology of prion disease

Answer 28

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

Question 29

features of new variant CJD (vCJD)

Answer 29

sporadic neuropsychiatric disorder
<45yrs
cerebellar ataxia + dementia
linked to BSE

Question 30

neuropathology of Alzheimers

Answer 30

• EC plaques (amyloid-beta)
• neurofibrillary tangles
• cerebral amyloid angiopathy (CAA)
• neuronal loss (cerebral atrophy)

Question 31

where is a-beta most toxic

Answer 31

intra-celularly

A-beta oligomers and protofibrils interfere with normal cell functions

Question 32

how does tau protein result in Alzheimers

Answer 32

maintains stability of the cytoskeleton
becomes hyperphosphorylated
accumulates inside the cell and causes cell death
Braak stags based on the location of tau pathology

Question 33

features of PD

Answer 33

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

Question 34

what are Braak stages used in PD

Answer 34

based on distribution of alpha-synuclein pathology
originates in the brainstem
anosmia = early sig
sleep disorders = prodrome

Question 35

what conditions can cause parkinsonism

Answer 35

idiopathic PD
drug-induced parkinsonism 
multiple system atrophy 
PSP
corticobasal degeneration 

*3 main DD =
MSA, CBD, PSP

Question 36

what is pick’s disease

Answer 36

fronto-temporal atrophy 
presents with frontal lobe pathology eg dysexecutive syndrome 
gliosis and neuronal loss 
balloon neurons 
tau-positive pick bodies

Question 37

difference between AD and CBD+ PSP on western blot of tau

Answer 37

AD - forms 3 bands
CBD+ PSP - 2 dense bands
Pick’s disease - 3R tauopathy

Question 38

features of fronto-temporal dementia

Answer 38

mutations in tau and progranulin

problems with TDP-43 (trafficking protein) = basis of some types of FTD