neurodegeneration Flashcards
If there is rapid neurodegeneration within a year, what do you think about?
Prion diseases
What are prion diseases?
A series of disease with common molecular pathology
The are no DNA or RNA transmissions
Only the protein itself is transmitted and causes infections
Prions = PRoteinaceous Ifections ONly
Kuru = a disorder endemic in papa new guinea
It was put down to endocanabalistic
Prion epidemic in cattle
What prions do we know?
Creutzfeldt-Jakob disease
Gerst-Sch….
Prion
Kuru
Histology of prion disease and what it is caused by
Spongiform tissue (holes in
host protein is changed by the infected protein -
alpha helix proteins normally present in us
can refold into beta pleated sheet; this can lead to an irreversible aggregation of the protein to form a pathological protein
vCJD - duration and link
Linked to infected bovine material
symptoms slightly longer than 1 year
Alzheimers pathological findings
Thinning of cortex
Widening of sulci
Widening of ventricles
Alzheimers
senile plaque proteins - beta amyloid proteins
tangles
Describe amyloid precursor proteins
beta protein is part of a precursor protein which is cleaved and then it
Normally it’s cut out
Parkinson’s disease symptoms
Akinesia
Describe the pathology in parkinsons
Lewy body dementia - inclusion of lewy bodies in the substantia nigra (should normally be black)
Neuromelanin - pigment sitting in dopaminergic neuron which project to striatum - loss of these cells cuases
Eosinophilic inclusions seen in H and E stains
What gene is associated with parkinson’s? Where is it found?
Alpha synuclein gene
Alpha synuclein is also found in peripheral ganglia
Parkinsonism can be mimicked by
Drugs
Vascular insufficiency in the basal ganglia
Multiple system atrophy (MSA) - also an alpha synuclein synopathy (glial)*
Corticobasal degeneration (CBD) - tau protein
Progressive supranuclear palsy (PSP)
Parkinsons alpha synuclein is
Tau-opathies
Pick’s disease
tau positive Pick bodies
Fronto-temporal atrophy
Gliosis and neuronal loss
Balloon neurons
Tau is important
gene on 17q21
16 exons
6 isoforms depending on post translational splicing which are normal
3R and 4R
tau is phosphorylated normally
if you dephosphorylated, you get six bands on the western blot
In PSP, you get 4R
Pick’s ????
Parkinsonism can be mimicked by
Drugs
Vascular insufficiency in the basal ganglia
Multiple system atrophy (MSA) - also an alpha synuclein synopathy (glial)*
Corticobasal degeneration (CBD) - tau protein
Progressive supranuclear palsy (PSP)
Parkinsons alpha synuclein is neuronal
