Alzheimer’s Disease Parkinson’s Disease Huntington’s Disease
Neurodegenerative disease, particularly of the cortex Movement disorder characterised by Autosomal dominant, neurodegenerative
symptoms of dementia (Poor memory + difficulty degeneration of DA neurones in the substantia
learning)
condition that involves repeated DNA
nigra part of the basal ganglia (controls sequence abnormal protein
Pathogenesis
Plaques movement + connects to motor cortex) movement disorders + cognitive
Amyloid precursor protein (APP) helps Progressive, adult-onset (mean age 65 yrs), M : F
impairment
neurones grow + repair after injury (2:1)
It gets used + recycled by α + γ secretase RF Pesticide exposure, DNA variants in LRRK2 Pathogenesis
soluble product gene Huntingtin (HTT) gene on Ch4
β- secretase produces an insoluble product contain a triplet repeat (CAG- which
creates a monomer (amyloid β) which are sticky + Aetiology Mutations in PINK1, PARKIN, α- codes for Glutamine
clump together = Plaques interrupt synapses + synuclein genes Polyglutamine disease)
neuronal communication
Tangles (inside cells) 10-35 repeats: Normal
Cytoskeleton (microtubules) held together by tau Caudate + >36 repeats: Huntington disease
proteins Putamen More repeats added = unstable =
β- amyloid plaque build up activates kinase = Striatum
early the onset of symptoms =
overly-phosphorylates tau proteins destabilises
+ forms neurofibrillary tangles Nigrostriatal Thalamus ANTICIPATION Earlier symptom
Ultimately pathway onset w/ each generation
Apoptosis of neuronal cells Helps initiate These repeats accumulate around
Atrophy of cortex + hippocampus movements the caudate + putamen neuronal
Gyri become narrower Calibrate +
Sulci + ventricles wider fine tune cell death
Biochemical changes = low ACh motor skills Affected areas = decreased GABA
Aetiology (DAergic) Pars and ACh, increased DA
Sporadic (90%) compacta
Late onset, gene (E4 allele of ApoE) Clinical features (Affected
ApoE helps break down β- amyloid Pars–‘pill rolling’ Signs + symptoms
1. Resting tremor
E4 makes it ineffective reticulata
2. Rigidity- ‘cogwheel’/ ‘lead pipe’ rigidity
Features typically develop after 35 years
Trisomy 21 on passive movement Progressive CNS involvement
APP gene found on Ch21 Movement Chorea + Athetosis
3. Brady/hypo/akinesia- ‘shuffling gait’
Increased risk of expression
(short steps + reduced arm movement) (can’t suppress, stops w/ sleep)
Familial
Early onset, dominant gene acquired 4. Postural instability (late) abnormal eye movements, poor
speeds regression No weakness unlike motor cortex/corticospinal coordination
Gene [PSEN-1 (Ch14) PSEN- 2 (Ch1)] both diseases Cognition
form subunits of γ secretase Mx Mood dementia, personality
These mutations change the location of the 1. If motor symptoms affecting QoL =
cleavage site different sized amyloid changes, depression
Levodopa (given with Carbidopa to
molecules Saccadic eye movements
prevent breakdown before it has passed
Mx
the BBB) Mx
1. 3 AChase inhibitors (Rx mild-moderate No Rx prevents progression
disease) 2. If motor symptoms are not affecting QoL
Donepezil, Galantanine, Rivastigmine = Dopamine agonist e.g. Bromocriptine/ Counselling for patient and family
2. NMDA receptor antagonist [Rx Levodopa/ MAO-B inhibitor e.g. Selegiline Patients usually die 10-20 years after Dx
moderate/contraindication to (1)] 3. COMT inhibitor e.g. Entacapone
Memantine
Neurodegenerative disease, particularly of the cortex Movement disorder characterised by Autosomal dominant, neurodegenerative
symptoms of dementia (Poor memory + difficulty degeneration of DA neurones in the substantia
learning)
condition that involves repeated DNA
nigra part of the basal ganglia (controls sequence abnormal protein
Pathogenesis
Plaques movement + connects to motor cortex) movement disorders + cognitive
Amyloid precursor protein (APP) helps Progressive, adult-onset (mean age 65 yrs), M : F
impairment
neurones grow + repair after injury (2:1)
It gets used + recycled by α + γ secretase RF Pesticide exposure, DNA variants in LRRK2 Pathogenesis
soluble product gene Huntingtin (HTT) gene on Ch4
β- secretase produces an insoluble product contain a triplet repeat (CAG- which
creates a monomer (amyloid β) which are sticky + Aetiology Mutations in PINK1, PARKIN, α- codes for Glutamine
clump together = Plaques interrupt synapses + synuclein genes Polyglutamine disease)
neuronal communication
Tangles (inside cells) 10-35 repeats: Normal
Cytoskeleton (microtubules) held together by tau Caudate + >36 repeats: Huntington disease
proteins Putamen More repeats added = unstable =
β- amyloid plaque build up activates kinase = Striatum
early the onset of symptoms =
overly-phosphorylates tau proteins destabilises
+ forms neurofibrillary tangles Nigrostriatal Thalamus ANTICIPATION Earlier symptom
Ultimately pathway onset w/ each generation
Apoptosis of neuronal cells Helps initiate These repeats accumulate around
Atrophy of cortex + hippocampus movements the caudate + putamen neuronal
Gyri become narrower Calibrate +
Sulci + ventricles wider fine tune cell death
Biochemical changes = low ACh motor skills Affected areas = decreased GABA
Aetiology (DAergic) Pars and ACh, increased DA
Sporadic (90%) compacta
Late onset, gene (E4 allele of ApoE) Clinical features (Affected
ApoE helps break down β- amyloid Pars–‘pill rolling’ Signs + symptoms
1. Resting tremor
E4 makes it ineffective reticulata
2. Rigidity- ‘cogwheel’/ ‘lead pipe’ rigidity
Features typically develop after 35 years
Trisomy 21 on passive movement Progressive CNS involvement
APP gene found on Ch21 Movement Chorea + Athetosis
3. Brady/hypo/akinesia- ‘shuffling gait’
Increased risk of expression
(short steps + reduced arm movement) (can’t suppress, stops w/ sleep)
Familial
Early onset, dominant gene acquired 4. Postural instability (late) abnormal eye movements, poor
speeds regression No weakness unlike motor cortex/corticospinal coordination
Gene [PSEN-1 (Ch14) PSEN- 2 (Ch1)] both diseases Cognition
form subunits of γ secretase Mx Mood dementia, personality
These mutations change the location of the 1. If motor symptoms affecting QoL =
cleavage site different sized amyloid changes, depression
Levodopa (given with Carbidopa to
molecules Saccadic eye movements
prevent breakdown before it has passed
Mx
the BBB) Mx
1. 3 AChase inhibitors (Rx mild-moderate No Rx prevents progression
disease) 2. If motor symptoms are not affecting QoL
Donepezil, Galantanine, Rivastigmine = Dopamine agonist e.g. Bromocriptine/ Counselling for patient and family
2. NMDA receptor antagonist [Rx Levodopa/ MAO-B inhibitor e.g. Selegiline Patients usually die 10-20 years after Dx
moderate/contraindication to (1)] 3. COMT inhibitor e.g. Entacapone
Memantine
