Neuro Pathology

Parkinson Disease

Loss of dopaminergic cells in substantia nigra pars compacta (in the basal ganglia) disrupts movement. Classic presentation is tremor, cogwheel rigidity, akinesia, postural instability, and shuffling gait. The condition is associated with Lewy bodies, which are aggregates of α-synuclein. 

Treatment:

levodopa

carbidopa

entacapone/tolcapone

selegiline

benztropine

bromocriptine, pramipezole, ropinirole

amantadine

Huntington Disease

Huntington disease is an autosomal dominant CAG repeat disorder on chromosome 4. This trinucleotide expansion can result in a gain-of-function that disrupts the normal transcriptional repression by huntingtin. This increases histone deacetylation (so increased transcriptional repression), silencing the genes necessary for neuronal survival. Condition is characterized by chorea, aggression, depression, and dementia.

Treatment:

tetrabenazine, reserpine

haloperidol

Alzheimer Disease
APP is usually degraded into A-α but in Alzheimer's, it is degraded into A-β amyloid forms seniles plaques. Neurofibrillary tangles formed from hyperphosphorlyated tau proteins, which are normally in the cytoskeleton.

Plaques will lead to widespread cortical atrophy, which can present as hydrocephalus ex vacuo. ApoE2 is associated with decreased risk, while ApoE4 is associated with increased risk. Alzheimer is also associated with APP, presenilin-1, and presenilin-2. 

Treatment:

memantine

donepezil, galantamine, rivastigmine

Frontotemporal Dementia

Inclusions of hyperphosphorlyated tau proteins form Pick bodies. Frontal lobe involvement results in behavioral changes. Temporal lobe involvement results in aphasia.

Lewy Body Dementia

Lewy bodies are aggregates of α-synuclein. Condition presents as dementia first, then parkinsonian symptoms.