AD General Flashcards
When looking at a brain, what is the tell tale sign that person had alzheimer’s?
severe degradation of temporal lobe
Beta-amyloid and alzheimer’s
Beta-amyloid protein is being overproduced, released into extracellular space, and interferes with synaptic function.
Two problems with overproduction of Beta-amyloid
- released in EC space and stops normal function
Explain the development of neurofibrillary tangles
Tau, a microtubule associated protein involved in transportation from cell body to axon terminal, get clogged in narrowing of cell body to axon.
Role of inflammation in AD?
local inflammatory response by activated microglia and astrocytes surrounding plaques can cause neurotoxicity
are Beta-amyloid plaques unique to AD?
no! found in a normal, aging brain. but prevalence and location is whats different.
where are neurofibrillary tangles and amyloid plaques most often found in alz?
strong density in temporal lobe (both medial and lateral portions)
the 2 “problems” of ApoE
ApoE can be turned into Beta amyloid and leave cell causing loss of synaptic function and eventual cell death.
ApoE can be turned into ApoE3/ApoE4 which can directly cause cell apoptosis
Presenilin1 and early onset AD
presenilin1 makes up a protein called gamma-secretase found in the rough ER and in the cell membrane.
Mutation of gamma-secretase in rough ER will cause increased Ca release, which causes cell death and destruction.
Changes in the Neurotransmitters of Alzheimer’s Brains
NE synthesis is reduced.
Cell loss and tangles in Locus Ceruleus.
Slight Dopamine reduction
Slight Serotonin reduction and tangles in Raphe cells
Reduction in Corticotrophin Releasing Factor
what is ApoE?
ApoE is normally secreted in high levels in neurons and microglia in response to damage
which signaling molecules are most affected in AD?
monoamine neuropeptides are affected
Most affected nt system in alz
acetylcholine system (ACh, AChE, ChAT)
Calcium and alz treatment?
Reduce calcium influx that contributes to cell death. problem is that Ca is involved in NT release and normal brain function
4 new alz treatment approaches
- Estrogens
why anti-oxidants as factor in AD treatment?
In cell cultures, beta-amyloid produces excessive free radicals that damage cellular membranes. This is prevented by vitamin E (an anti-oxidant)
anti-inflammatory drugs and AD?
Reduced Alzheimer’s incidence among arthritis patients chronically using aspirin, ibuprofen.
Calcium and AD treatment?
Reduce calcium influx that contributes to cell death. problem is that Ca is involved in NT release and normal brain function
Main genetic risk factors for AD
- APP
- Presenilins (active components of the gamma-secretase complex; PSEN 1 & PSEN 2)
- ApoE polymorphism (which type?)
Proportion of patients with dementia, who are said to suffer from AD:
- ca. 60%
Number of people with AD worldwide
- ca. 20 mil
Proportion of AD cases explained by genetic risk factors:
- ca. 3%
Where does tau pathology usually begin?
- in the entorhinal cortex
Proportion of people with amyloid deposits but no AD symptoms
- 15-25% of subjects in PET scans show the same amount of amyloid deposits and no sympoms (Mormino et al., 2009)
