L3 Pathology of Dementias Flashcards
how to do brain donation
frozen hemisphere –> brass plates for rapid freezing and stored at -80degreesc.
fixed hemisphere –> fixed for 3 weeks in formalin
what is the process during immunohistochemistry
process brain into wax
then remove wax from sections by xylene
stain areas of interest
tag with antibodies that recognise
what do we look for down the microscope
abnormalities
cell types involved
regions of brain affected
what are some glial cells
microglia, astrocytes, oligodendrocytes
what are neurons and how are messages transmitted
electrically excitable cell that receives, processes and transmits info through electrical and chemical signals
messages transmitted through synapses
what are some specialised neurons
sensory
motor
interneurons
what is the structure of neurons
cell body (nucleus and cytoplasm), dendrites, axon
what is the function of astrocytes
provide nutrients to nervous tissue
envelop synapses made by neurons
in blood brain barrier
what is the function of microglia
maintenance of CNS
inflammation
survey brain and react to any abnormalities
resident macrophages
what is the function of oligodendrocytes
support and insulation to axons
myelinate axons
what are 3 genes involved in alzheimers
AbetaPP chromosome 21
Presenilin-1 (14)
Presenilin-2(1)
what is the % of inherited forms in AD
<5%
what are macroscopic features of AD
enlarged ventricle
hippocampal atrophy, hippocampus stained with a beta antibody
-extracellular amyloid plaues formed between cells
-blood vessels in brain covering leptomeninges, build up of Abeta within cells CAA
what is the link with abeta in AD and what is it produced from
=produced from cleavage of the amyloid precursor protein
- mutations in the AbetaPP gene cause AD, implicating APP metabolism
- depending on where the mutations are located influence pathological and biochemical hallmarks (e.g. if we have mutations in the middle of the A beta peptide, see more Abeta deposition in the blood vessels compared to other mutations where we see more plaques)
summarise what tau does in AD
- positive in nerve cells
- a microtubule associated binding protein
- 6 tau isoforms expressed adult human brain
- equal amounts of 3R and4R tau in healthy
- tau twice as high in GM to WM
- hyperphosphorylated pathologically
- use electron microscopy to see
what diagnostic criteria can be used for AD to assess neuropathology
Distribution of amyloid plaques - Thal phases; 0 to 5
Distribution of Tau pathology - Braak and Braak staging; 0 to 6
Neuritic plaque frequency - CERAD score; none to frequent (in 3 different cortical regions)
how many stages are there in the thal phases and how are they divided
what do you look at in the different phases
pre-clinical - phase 1,2,3
1- look for amyloid plaques in the 4 regions and cortex
2- look for beta deposition in the hippocampus
3- look for a-beta deposition in the basal ganglia/striatum
clinical - phase 4,5
4- look for a-beta in substantia nigra
5 - look for deposition in cerebellum
who describes the pattern of progression of neurofibrillary tangles (NFT) and what are the stages?
Braak & Braak
stage I-II: NFTs in mediotemporal lobe/Transentorhinal structures
stage III-IV: NFTs in Limbic structures
Stage V-VI: NFTs numerous in isocortex
how is the CERAD diagnosis of AD graded
done by eye when neuropathologist looking at frequency of cord plaques
graded from spare-moderate-frequent
which three major clinical syndromes is frontotemporal dementia present with?
behavioural FTD
semantia dementia
progressive non-fluent aphasia
what is the 2nd most common dementia and what is the gender distribution
frontotemporal dementia (under age 65)
equal gender distribution
what are additional clinical symptoms of ftd
motor neuron disease/amyotrophic lateral sclerosis
corticobasal syndrome
progressive supranuclear palsy
what % of frontotemporal dementia is inheritable
30-50%
what mutations are in 3 genes in ftd
progranulin
microtubule-associated protein
chromosome 9 open reading frame 72 (C9orf72)