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Pathology (Guide) > Histopathology - Neurodegenerative Diseases > Flashcards

Histopathology - Neurodegenerative Diseases Flashcards

1
Q

What are neurodegenerative diseases?

A

Progressive, irreversible conditions leading to neuronal loss

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2
Q

What is the common pathogenic mechanism for neurodegenerative disease?

A

Accumulation of misfolded proteins which may be intra- or extracellular

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3
Q

What is dementia?

A
  • A global impairment of cognitive function + personality withouth impairment of consciousness.
  • Impairment goes beyond what mught be expected from normal ageing.
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4
Q

What are the components of dementia?

A
  • Memory impairment + atleast one cognitive disturbance:
  • Aphasia
  • Apraxia
  • Agnosia
  • Disturbance in executive functioning
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5
Q

What is aphasia?

A

Language disorder

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6
Q

What is apraxia?

A

Loss of ability to carry out learned purposeful tasks

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7
Q

What is anomia?

A

The loss of ability to recall/find words

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8
Q

What is agnosia?

A

Loss of ability to recognise objects, people etc.

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9
Q

What are the 5A’s associated with dementia?

A
  • Amnesia
  • Apraxia
  • Aphasia
  • Agnosia
  • Anomia
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10
Q

What are the most to least common types of dementia?

A
  • Alzheimers
  • Vascular
  • Lewy body
  • Fronto-temporal
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11
Q

What is the onset of Alzheimer’s disease?

A

> 50yrs

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12
Q

How is Alzheimer’s diagnosed?

A

Clinically
- PET/MRI may help

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13
Q

What is the pathophysiology of Alzheimer’s disease?

A
  • Accumulation of β-amyloid deposits outside nerines
  • Leads to senile plaques that interfere with neuronal communication
  • Hyperphosphorylation of Tau protein
  • Leads to dissociation from neurine microfilaments and accumulation into neurofibrillary tangles
  • Causes cerebral atrophy
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14
Q

What are the radiological findings of Alzheimer’s disease?

A
  • General brain atrophy
  • Widened sulci
  • Narrowed gyri + enlarged ventricles: medial temporal lobes + hippocampus = loss of cholinergic neurones
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15
Q

What is seen on histology for Alzheimer’s disease?

A
  • Senile plaques of β-amyloid protein
  • Neurofibrillary tangles of tau protein
  • Cerebral amyloid angiopathy
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16
Q

What is the staging system used for Alzheimer’s?

A

BRAAK Staging

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17
Q

What is the treatment for Alzheimer’s Disease?

A

Symptomatic:
- Anti-cholinesterases
- nAChR agonists
- Glutamate antagonists

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18
Q

What is the pathophysiology of Vascular dementia?

A
  • Neuronal death due to infarcts of small + medium sized vessels
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19
Q

What are the symptoms of Vascular dementia?

A
  • Step-wise deterioration
  • Sx reflect area of brain affected
20
Q

What are some RFs for Vascular dementia?

A
  • Atherosclerosis
  • Obesity
  • Smoking
  • Alcohol
  • Diabetes
  • Unhealthy diet
  • Sedentary lifestyle
21
Q

What are the symptoms of Lewy body dementia?

A
  • Psychological disturbances occur early
  • Day-to-day fluctuations in cognitive performance + alterness
  • Visual hallucinations (little people/animals running around)
  • Spontaneous motor signs of Parkinsonism
  • Recurrent falls + syncope
  • Aggression
22
Q

What is the pathology of Lew body dementia?

A

Pathologically indistinguishable from Parkinson’s

23
Q

What areas of the brain are affected in fronto-temporal dementia?

A
  • Only frontal + temporal lobes (Atrophy)
24
Q

What is seen on histology of fronto-temporal dementia?

A

Pick bodies
- Hyperphosphorylated tau

25
Q

What mutations are associated with Lewy body dementia?

A

Progranulin gene

26
Q

What is the onset of Lewy body dementia?

A
  • Strong FHx
  • Younger people (40-60yrs)
27
Q

What are some symptoms associated with Lewy body dementia?

A
  • Personality change
  • Disinhibition
  • Overeating
  • Emotional blunting
28
Q

What is Parkinson’s disease?

A

Progressive depletion of dopaminergic neurones in the nigrostriatal pathway from substantia nigra in basal ganglia to striatum
- Leads to widespread motor deficits

29
Q

What is the pathophysiology of Parkinson’s disease?

A
  • Lewy bodies present in affected neurones
  • Α-synuclein is main component of Lewy bodies
  • Mutations in Α-synuclein cause Parkinson’s
30
Q

Where are Α-synuclein deposits found?

A
  • Lewy bodies (in neurones)
  • Peripheral ganglia (motor retardation)
  • Olfactory bulb (Early loss of smell)
31
Q

What are the cardinal signs of Parkinson’s?

A

TRAP
- T: Tremor
- R: Rigidity
- A: Akinesia
- P: Postural instability

+ Psychiatric features in later disease:
- Dementia
- Hallucinations
- Anxiety

32
Q

What are some Parkinson Plus Syndromes?

A
  • Lewy body dementia
  • Progressive supranuclear palsy
  • Corticobasal syndrome
  • Multiple system atrophy
  • Vascular parkinsonism
  • Drug-induced
33
Q

What is Progressive Supranuclear Palsy and its features?

A

Tauopathy with limited vertical gaze (downgaze)
- Early falls
- Axial rigidity
- Akinesia
- Dysarthria
- Dysphagia

34
Q

What is Corticobasal Syndrome and its features?

A

Tauopathy with varied presentation
- Unilateral parkinsonism
- Dystonia/myoclonus
- Apraxia +/- ALIEN LIMBS phenomenon
- ?Progressive non-fluent aphasia

35
Q

What is Mutliple System Atrophy and its features?

A

Synucleinopathy
- Early autonomic dysfunction
- Cerebellar predominant (MSA-C)
- Parkinsonism predominant (MSA-P)

36
Q

What are some features of Drug-induced Parkinsonism?

A

Bilateral Sx

37
Q

What misfolded pathological proteins are associated with Alzheimer’s disease?

A
  • Tau
  • Β-amyloid
38
Q

What misfolded pathological proteins are associated with Lewy body Dementia?

A
  • Α-synuclein
  • Ubiquitin
39
Q

What misfolded pathological protein is associated with Corticobasal degeneration?

A

Tau

40
Q

What misfolded pathological protein is associated with Frontotemporal dementia (linked ot Chr 17)?

A

Tau

41
Q

What misfolded pathological protein is associated with Pick’s disease?

A

Tau

42
Q

What is Prion Disease?

A

A series of diseases with common molecular pathology often caused by infection + transfer of proteins from organism to host (rather than RNA/DNA)

43
Q

What are the different types of Prion Diseases and their incidences?

A

Sporadic (80%):
- Creutzfeld-Jakob disease

Acquired (<5%):
- Kuru
- Variant CJD
- Iatrogenic CJD

Genetic (15%):
- Gerstmann-Straussler-Scheinkler Syndrome (GSS)
- Fatal Familial Insomnia

44
Q

What is a feature of Creutzfeld-Jakob disease?

A

Rapid <1yr decline

45
Q

What is a feature of Kuru Disease?

A

Cannibalism

46
Q

What is a feature of Variant CJD?

A

Linked ot bovine spongiform encephalopathy (e.g. mad cow disease)

47
Q

What is a feature of Iatrogenic CJD?

A

Following flood transfusions of surgical procedures

Pathology (Guide) (84 decks)

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