Neurodegeneration Flashcards
what is the New Variant CJD (vCJD)? epidemiology? presentation?
Sporadic neuropsychiatric disorder
Patients <45 yrs old Cerebellar ataxia Dementia Longer duration than CJD Linked to BSE - bovine spongiform encephalopathy Diagnosed at autopsy since 1990
what is required to diagnose alzheimers?
Extracellular plaques
Neurofibrillary tangles
+ symptoms are needed for diagnosis
other features:
Cerebral amyloid angiopathy (CAA)
Neuronal loss (cerebral atrophy)
spongiform changes in the brain are seen in which condition?
which other findings will be seen? why?
Prion
will also see prion protein deposits - prion protein is usually in a structure, it unfolds and forms B structure. this process keeps happening. no1 knows what causes it.
what is the common mechanism of these neurodegenerative disorders?
prion type spread - where protein changes it shape
most common neurodegenerative disorder?
alzheimers
list some imaging findings for Alzheimers?
Cortical atrophy - especially temporal lobe
Senile plaques - (a beta- AB proteins forming tangles or amyloid plaques stained brown) on silver stain
Cerebral amyloid angiopathy
Tau proteins?
AB - A beta proteins are formed via what process?
APP processing - amyloid precursor proteins
what is Tau? relevance in alzheimers?
cytoskeletal protein
becomes hyperphosphorylated in AD
Alzheimers - 3R + 4R tauopathy
where is the earliest appearance of tau pathology? where does its course go? how do we characterise this?
anterior hippocampus
the spread to posterior h. then into temporal lobe. then occipital.
this is called the Braak staging - thee further the spread, the higher the stage
what is the aetiology behind CTE - chronic traumatic encephalopathy?
tau pathology
is similar to alzheimers but not the same.
caused by repetitive trauma to the head
what is the definitive lesion in Parkinson’s?
lewy body in substantia nigra
what is the most common lewy body disease?
parkinsons
what is the locus of pathology in parkinsons?
substantia nigra
loss of dopaminergic cells* = loss of pigment / pale
which usually project from SN to basal ganglia
what is the diagnostic gold standard in parkinsons?
α-synuclein immunostaining is considered as the diagnostic gold standard
as they react with lewy bodies and lewy neurite
braak can also be used to stage?
parkinsons
the following conditions present with Parkinsonism, what proteins are they associated with;
Multiple system atrophy
Progressive supranuclear palsy
Corticobasal degeneration
Multiple system atrophy – a synuclein (affects glial cells)
Progressive supranuclear palsy - tau*
Corticobasal degeneration - tau
ALPHA SYNUCLEINism - idiopathic Parkinsons!!!
*4R tauopathy
briefly how can you tell the difference between alzhiermers and Frontotemporal dementia’s?
alzhiemers - more a temporal/ memory disorder
FTD - mood and behaviour disorder
what is Pick’s disease? presentation?
what protein is present?
characteristic findings?
Fronto-temporal atrophy
is a type of frontotemporal dementia
Marked gliosis and neuronal loss
Balloon neurons
Tau positive Pick bodies - 3R Tauopathy
Presentation: Mood change, aggression, disinhibition
what are the genetics in FTDP-17 (frontotemporal dementia) syndromes?
Autosomal dominant
Abundant TAU pathology
> 20 pathogenic mutations identified
Missense and splicing mutations
what is the structure of tau?
Single gene on 17q21
16 exons
Alternative splicing gives rise to 6 isoforms
3R or 4R-tau (microtubule-binding domains)
Two further inserts with unknown function
Shortest form (3R/0N) foetal
what can lead to tau negative frontotemporal dementia?
Progranulin gene mutation
on chromosome 17
Some FTPD not tau positive but are progranulin positive
what is the pathological classifciation of frontotemporal dementias?
Tauopathies:
3R Tau - Picks disease
4R Tau - PSP (progressive supranu…)
3R + 4R Tau - Alzheimers
Tau negative FTLD:
TDP-43 +- ones
FUS associated ones
