what do most neurodegenerative diseases have in common
development of different abnormal protein aggregates that are resistant to degradation by normal cellular mechanisms
why is down syndrome strongly associated with alzheimers disease
APP gene is on chromosome 21 of which they have 3, this gene predisposes to alzheimers
whats the fundamental aspect of alzheimers disease
EXTRAcellular deposition of amyloid beta peptide
where do the amyloid beta peptides come from
derived from enzymatic cleavage of amyloid precursor protein, APP.
when this cleavage is amyloidogenic it makes the AB proteins
what is an amyloid
an extracellular deposit of an insoluble fibrillar protein that leads to tissue damage and functional compromise
what makes the tau proteins form
the inflammatory reaction to the amyloid beta peptides is what causes the altered phosphorylation and aggregation
what happens grossly to the morphology of the brain on an alzheimers
diffuse cerebral atrophy with widened sulci, narrowed gyri, and ventricular enlargement
what are the two histological hallmarks of alzheimers
neurofibrillary tangles - intracellular,
neuritic plaques - extracellular
what happens to blood vessels of the brain in alzheimers
cerebral amyloid angiopathy
what is cerebral amyloid angiopathy
where the cerebral blood vessels are affected by amyloid deposition. become thickened
what things are specific to alzheimers disease
amyloid beta is specific to alzheimers
what is huntingtons
a mutation in the HD gene resulting in an increase in CAG repeats.
disease occurs when the number of repeats is 40 or more with formation of intraneuronal inclusions of huntington protein
what is the morphology of huntingtons
atrophy of the caudate, diffuse cortical atrophy, dilation of the ventricles
what is the microscopic appearance of huntingtons disease
intranuclear inclusions of huntington protein
neuronal loss in the striatum
what is prion disease
a group of conditions in which dementia develops due to neurodegeneration caused by abnormal confromations of normal cellular protein called prion protein
how do prions arise
they arise through spontaneous conformational change from its normal isoform. or through mutations in the gene which encodes PrPc - PRNP
whats the prion disease in humans
CJD
pathogenesis of prions
prions are able to bind to normal PrPc and induce a conformational change which gives rise to new prions - this is how they reproduce. they then accumulate forming aggregates which leads to dementia
gross morphology of the brain on CJD
there is none or little atrophy
microscopic appearance of CJD
spongiform transformation of the cortex and vacuiles
neuronal loss, coalescence of vacuolar spaces into larger cystic spaces
whats the hall mark of CJD what does it look like
spongiform transformation
many small empty appearing vacuiles within the neuropil and the cytoplasm of neurones
what is vascular dementia
when patients suffer many TIAs and several small stroke thus developing cognitive impairment
its an accumulation of deficieits through multiple infarcts
