Histopathology - Neurodegenerative Diseases Flashcards
What are neurodegenerative diseases?
Progressive, irreversible conditions leading to neuronal loss
What is the common pathogenic mechanism for neurodegenerative disease?
Accumulation of misfolded proteins which may be intra- or extracellular
What is dementia?
- A global impairment of cognitive function + personality withouth impairment of consciousness.
- Impairment goes beyond what mught be expected from normal ageing.
What are the components of dementia?
- Memory impairment + atleast one cognitive disturbance:
- Aphasia
- Apraxia
- Agnosia
- Disturbance in executive functioning
What is aphasia?
Language disorder
What is apraxia?
Loss of ability to carry out learned purposeful tasks
What is anomia?
The loss of ability to recall/find words
What is agnosia?
Loss of ability to recognise objects, people etc.
What are the 5A’s associated with dementia?
- Amnesia
- Apraxia
- Aphasia
- Agnosia
- Anomia
What are the most to least common types of dementia?
- Alzheimers
- Vascular
- Lewy body
- Fronto-temporal
What is the onset of Alzheimer’s disease?
> 50yrs
How is Alzheimer’s diagnosed?
Clinically
- PET/MRI may help
What is the pathophysiology of Alzheimer’s disease?
- 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
What are the radiological findings of Alzheimer’s disease?
- General brain atrophy
- Widened sulci
- Narrowed gyri + enlarged ventricles: medial temporal lobes + hippocampus = loss of cholinergic neurones
What is seen on histology for Alzheimer’s disease?
- Senile plaques of β-amyloid protein
- Neurofibrillary tangles of tau protein
- Cerebral amyloid angiopathy
What is the staging system used for Alzheimer’s?
BRAAK Staging
What is the treatment for Alzheimer’s Disease?
Symptomatic:
- Anti-cholinesterases
- nAChR agonists
- Glutamate antagonists
What is the pathophysiology of Vascular dementia?
- Neuronal death due to infarcts of small + medium sized vessels
What are the symptoms of Vascular dementia?
- Step-wise deterioration
- Sx reflect area of brain affected
What are some RFs for Vascular dementia?
- Atherosclerosis
- Obesity
- Smoking
- Alcohol
- Diabetes
- Unhealthy diet
- Sedentary lifestyle
What are the symptoms of Lewy body dementia?
- 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
What is the pathology of Lew body dementia?
Pathologically indistinguishable from Parkinson’s
What areas of the brain are affected in fronto-temporal dementia?
- Only frontal + temporal lobes (Atrophy)
What is seen on histology of fronto-temporal dementia?
Pick bodies
- Hyperphosphorylated tau
What mutations are associated with Lewy body dementia?
Progranulin gene
What is the onset of Lewy body dementia?
- Strong FHx
- Younger people (40-60yrs)
What are some symptoms associated with Lewy body dementia?
- Personality change
- Disinhibition
- Overeating
- Emotional blunting
What is Parkinson’s disease?
Progressive depletion of dopaminergic neurones in the nigrostriatal pathway from substantia nigra in basal ganglia to striatum
- Leads to widespread motor deficits
What is the pathophysiology of Parkinson’s disease?
- Lewy bodies present in affected neurones
- Α-synuclein is main component of Lewy bodies
- Mutations in Α-synuclein cause Parkinson’s
Where are Α-synuclein deposits found?
- Lewy bodies (in neurones)
- Peripheral ganglia (motor retardation)
- Olfactory bulb (Early loss of smell)
What are the cardinal signs of Parkinson’s?
TRAP
- T: Tremor
- R: Rigidity
- A: Akinesia
- P: Postural instability
+ Psychiatric features in later disease:
- Dementia
- Hallucinations
- Anxiety
What are some Parkinson Plus Syndromes?
- Lewy body dementia
- Progressive supranuclear palsy
- Corticobasal syndrome
- Multiple system atrophy
- Vascular parkinsonism
- Drug-induced
What is Progressive Supranuclear Palsy and its features?
Tauopathy with limited vertical gaze (downgaze)
- Early falls
- Axial rigidity
- Akinesia
- Dysarthria
- Dysphagia
What is Corticobasal Syndrome and its features?
Tauopathy with varied presentation
- Unilateral parkinsonism
- Dystonia/myoclonus
- Apraxia +/- ALIEN LIMBS phenomenon
- ?Progressive non-fluent aphasia
What is Mutliple System Atrophy and its features?
Synucleinopathy
- Early autonomic dysfunction
- Cerebellar predominant (MSA-C)
- Parkinsonism predominant (MSA-P)
What are some features of Drug-induced Parkinsonism?
Bilateral Sx
What misfolded pathological proteins are associated with Alzheimer’s disease?
- Tau
- Β-amyloid
What misfolded pathological proteins are associated with Lewy body Dementia?
- Α-synuclein
- Ubiquitin
What misfolded pathological protein is associated with Corticobasal degeneration?
Tau
What misfolded pathological protein is associated with Frontotemporal dementia (linked ot Chr 17)?
Tau
What misfolded pathological protein is associated with Pick’s disease?
Tau
What is Prion Disease?
A series of diseases with common molecular pathology often caused by infection + transfer of proteins from organism to host (rather than RNA/DNA)
What are the different types of Prion Diseases and their incidences?
Sporadic (80%):
- Creutzfeld-Jakob disease
Acquired (<5%):
- Kuru
- Variant CJD
- Iatrogenic CJD
Genetic (15%):
- Gerstmann-Straussler-Scheinkler Syndrome (GSS)
- Fatal Familial Insomnia
What is a feature of Creutzfeld-Jakob disease?
Rapid <1yr decline
What is a feature of Kuru Disease?
Cannibalism
What is a feature of Variant CJD?
Linked ot bovine spongiform encephalopathy (e.g. mad cow disease)
What is a feature of Iatrogenic CJD?
Following flood transfusions of surgical procedures
