Dementia Flashcards
(28 cards)
Define the technique eImmunohistochemistry
this technique uses antibodies to visualise plaques in the ND brain.
where are tau and AB plaques located
tau : inside the neuron
AB : outside the neuron
what is the role of APP in Alzheimer’s
The beta and gamma secretase of this protein secretes AB oligomers.
which two toxic AB oligomers are present in AD
AB-40 :
AB-42 : dangerous
Define tau hyperphosphorylation
Tau binds to the microtubules in the cell and stabilises it. In ND’s tau can be phosphorylated which results in the release from these microtubules.
Hyperphosphorylation of tau leads to aggregation inside the neuron and destabilisation.
what is the genetic evidence for causal role of AB oligomers
in Down syndrome there is evidence of AD pathology at 40-50 since there is an extra copy op APP producing chromosome.
this gives a higher risk to AD
what is the most common cause of FAD (familial AD)
Mutations in presenilin (Presenilins (PSs) are the catalytic core of γ-secretase complex.)
- -> increases AB-42.
- -> directly involved in the formation of AB
which protein is part of the gamma-secretase complex
PSEN1 in AD
Presenilin 1 deficiency inhibits Aβ formation
AB oligomers inhibit LTP
aggregates AB bad ones
what is a late-onset risk factor for AD
APOE, it is directly involved in the clearing of AB.
what are the autosomal dominant forms of AD
what are the sporadic forms of AD
autosomal dominant forms of AD –> PSEN1, PSEN2, APP gene
sporadic forms of AD –> diet, age, head trauma, etc
is there a positive mutation in the APP gene for AD?
Yes, there is a mutation which decreases the affect of gamma and beta secretase, preventing AB formation.
Arctic mutation in APP:
- Aβ decreased
- Increased formation of protofibrils
is tau required for AB toxicity?
yes.
Define the AB hypothesis cascade
- overproduction/decreased clearance AB-42
- AB-42 oligomerization
- subtle effects of AB-42 on synapses
- neuroinflammation
- synaptic injury
- altered neurohomeostasis
- ROS production
- cell death
- dementia.
what is FT(L)D
frontotemporal dementia
what are the criteria of bvFTD (behavioral variant of Frontotemporal dementia (bvFTD))
- disinhibited behaviour
- apathy
- loss of sympathy
- compulsive behaviour
–> Memory is spared in FTD
what is a specific feature of FTD
degeneration (atrophy) of the frontal lobe
what are important inducers/mutations of FTD
what are important inducers/mutations of AD
AD:
- APP
- PSEN1
FLD:
- TAU
- TDP-43 (ALS)
- C9ORF72 (ALS)
what is the genetic cause of neurodegenration
genetic variants of FED are often associated with PD and MND (motto neuron diseases)
how many isoforms of Tau are there, with how many binding domains
6, varying between 3-4 binding domains.
the isoforms with 3 binding domains bind less powerfully with microtubules.
what is the cause of genetic FTD-tau forms
single amino acid missense mutation clustered on a specific axon.
which tau isoforms are found in AD and in FLD?
AD: 3R-4R
FLD: only 4R
which tau aggregate induced toxicity
the oligomeric precursor tau, these result in neuronal loss
do you need tau inclusions to form a toxic phenotype
NO, the oligomers are more toxic than the fibrils (fibrils are inclusions).
Synapse loss (and microglial activation) precede tau inclusions
