CNS degeneration Flashcards
Really rapid neurodegeneration
Spongiform vacuolation
Suspect Prion disease
Cortical atrophy - widening sulci, gyra shrinkage, ventricular enlargement
Hippocampus affected
Beta-amyloid plaques +Tau tangles
Most common neurodegenerative disease
Alzheimer’s disease
Beta-amyloid plaques Tau tangles (Tau hyper-phosphorylation)
Alzheimer’s disease
Pattern of Tau tangle formation
Braek staging
Hippocampus (I-III) > temporal (IV) > occipital (peri-striated cortex (V) then striate cortex (VI) ‘HTO’
Braek staging
AD staging - based on location of Tau tangles using Tau immunostaining
I-VI
Braek stages I-III
Hippocampus only
Braek stage V
Occipital lobe (peri-striatal)
Braek stage VI
Occipital lobe (striatal)
Braek stage at which symptoms start to appear
III or IV
Tau immunostaining in peristriate cortex but not striate cortex is consistent with which Braak grading?
Braek V
Contact sports
Tauopathy
Chronic traumatic encephalopathy
Alpha-synuclein ‘smooth hyaline inclusions’ in substantia nigra (SN) + cortex
Cortex = cognitive changes
SN = dopaminergic cell death = Parkinson’s symptoms
Lewy Body dementia
Function of dopaminergic neurons
Project from SN to basal ganglia
Death = Parkinson’s triad (bradykinesia, pill-rolling tremor, rigidity)
Discolouration of SN
Dopaminergic cell death
Pattern of Lewy Body formation
Also Braek staging:
Medulla (I) > Pons (II) > SN (III) > Basal forebrain (IV) > Cortex (V)
‘Many People See Blue Cats’
What is interesting about the spread of Lewy Body formation?
Initial symptoms of LBD are due to SN pathology (Parkinsonism) but LB initially form in medulla. Sleep disorders due to LB in pons may be an initial prodrome to look out for
When do symptoms of LBD occur?
60-70% SN dopaminergic death
Alpha-synuclein (+ ubiquitin) in dopaminergic cells of cortex + SN
Fluctuating cognition, visual hallucinations, Parkinsonism, recurrent falls + syncope
Lewy Body Dementia
Proteinopathies causing Parkinsonism
Lewy Body Dementia (LBD) - Alpha-synuclein
Multiple system atrophy (MSA) - Alpha-synuclein
Progressive Supranuclear Palsy (PSP) - Tau
Corticobasal degeneration (CBD) - Tau
Alpha-synuclein
Glial cells
Parkinsonism
MSA
Multiple system atrophy
Tau
Downward gaze, Parkinsonism
PSP (Progressive Supranuclear Palsy)
Tau
Unilateral Parkinsonism, myoclonus, alien limbs
CBD (Cortico-basal degeneration)
Think weird cannabinoids
Parkinsonism symptoms
TRAP
Tremor, rigidity, akinesia / bradykinesia, postural instability
Tau in fronto-temporal lobes
Loss of executive function - disinhibition, cognition ‘pick up girls’
Pick’s disease (type of frontotemporal dementia)
Tauopathy classification
Pick’s disease (3R)
CBD, PSP (4R)
Alzheimer’s disease (3R and 4R)
Tau gene
Pro-granulin (chromosome 17)
Cat’s eye inclusions
Mutations in pro-granulin
3R + 4R Tauopathy
AD
4R Tauopathy
CBD, PSP
3R Tauopathy
Pick’s disease
Early onset AD
Down’s Syndrome
Reduced uptake on DAT scan
Parkinson’s
Demyelinating plaques
Myelin basic protein
Proteo-lipid protein
MS
4 stages of MS plaque
- Acute (oedema)
- Early chronic (oedema + macrophages, some myelin breakdown)
- Late chronic active (complete myelin loss, macrophages still present)
- (complete myelin loss, no macrophages)
