(3.7) Patho and Pharmacology of Alzheimer's and other Dementias Flashcards
(46 cards)
What are the cardinal signs of Alzheimer’s?
Brain shrinkage, senile plaques, neurofibrillary tangles
What is the ratio of females to males that have AD?
2:1 female to male
What are the sxs of AD?
- Memory loss (esp recent mem)
- Impaired ability to learn, reason
- Impaired ability to carry out ADLs
- Confusion, untidiness
- Anxiety, suspicion, hallucinations
- Motor dysfunction in late stage disease
What are environmental risk factors for AD?
- Age
- Low educational level
- Reduced mental activity in late life
- Reduced physical activity in late life
- Risks for vascular disease
- Head injury
What is the neuropathology of AD in simplest terms?
Loss of brain volume
What is present in the brains of AD pts?
Amyloid plaques and neurofibrillary tangles
Where are amyloid plaques?
Extracellular
What do amyloid plaques consist of?
Amyloid-beta peptide (AB)
Where are neurofibrillary tangles?
Intracellular
What do neurofibrillary tangles consist of?
Hyper-phosphorylated tau
What parts of the brain does earlier stage AD start at?
- Entorhinal complex (memory formation/consolidation)
- Basal forebrain cholinergic systems (learning)
To what parts of the brain does AD spread to?
- Hippocampus (memory formation/consolidation)
- Neocortex (memory, learning, cognition)
What is a striking feature of neurons w NFT and/or in vicinity of plaques?
Destruction of synapses
What does synapse loss result in?
Reduced levels of neurotransmitters esp ACh, but also serotonin, NE, DA
What is another consequence of synapse loss?
Dysregulated glutamate which causes excess excitotoxicity and neurotoxicity
Regarding AB, what is linked to early onset AD?
- Mutations in the gene encoding the AB precursor protein (APP)
- Mutations in the gene encoding presenilin proteins involved in cleaving AB from APP
What is the connection between Down’s syndrome and AD?
- Trisomy 21 is associated w an AD-like phenotype in 4th decade of life
- APP gene is located on chromosome 21
What does NFT formations result in?
Cytoskeletal defects
What happens at unhealthy microtubules where tangles have accumulated?
Cytoskeletal tracks are disrupted and disorganized, resulting in defects in axonal transport that lead to synaptic dysfunction
In addition to causing damage to the neurons directly, what else is AB thought to do?
Induce neurotoxicity indirectly by triggering microglial activation
Why does AB induce microglial activation?
Process aimed at clearing the amyloid from the brain
What do activated microglia release that causes damage?
- Proinflammatory cytokines (e.g. prostaglandins, interleukins, tumor necrosis factor alpha) that cause neuroinflammation
- Reactive nitrogen and oxygen species that cause oxidative stress
What is ApoE?
Responsible for transporting cholesterol in brain
What can altered ApoE function do?
Can affect AB aggregation or clearance
