Wed 11/04 AD and Dementia Flashcards
True or False: Alzheimer’s disease (AD) is the same thing as Alzheimer’s dementia.
False
They are related but not synonnymous. Alzheimer’s disease (AD) is the disease that leads to Alzheimer’s dementia.
*Using AD throughout the rest of the cards instead of typing out Alzheimer’s disease.
What is AD?
Where does it start?
- A progressive neurodegenerative disorder of cholerinergic neurons characterized by loss of memory and severe decline in intellectual function.
- Results in widespread inflammation and death of cholinergic cells in the limbic system
- Starts in temporal lobe around hippocampal formation
True or False: Age is a major risk factor for developing AD but it is not the same as age related forgetfullness.
True
What does hyperphosphorylated mean?
Lots of phosphates-as in attached to something, like a protein
How is an AD diagnosis confirmed?
Autopsy which will show two things
- Amyloid plaques accumulated extracellularly
- Tau protein became hyperphosphorylated and accumulated intracellularly.
What is the normal function of tau proteins?
stabilize the cellular cytoskeleton
If you lose the stability of the cytoskeleton in neurons, what happens? (4)
- lose cell structure/function
- lose anterograde transport in neurons
- lose retrograde transport in neurons
- cell will die
2 Points about familial AD
- uncommon
- onset age 35-50
Biggest risk factor for AD
Age
Two hypotheses regarding the cause of AD
- A Beta hypothesis- Amalyiod Precursor Protein- function is not totally known, extracellular, protein gets cleaved and can get cleaved incorrectly, becomes difficult to clear out the messy proteins in aging process; build up over time.
- Tau protein- normally support the cytoskeleton and micrtubules, intercellular, get oodles of phosphates stck to them and start to clump up, things fall apart inside the cell
* now they are thought to cause the inflammation
Amyloid Cascade from Mans PP (9)
Warning: Really technical language ahead
- Overproduction, decreased clearance or enhanced aggregation of Aß42
- Aß42 oligomerization and and deposition as diffuse plaques
- Subtle effects of Aß42 oligomers on synapses
- Microglial and astrocytic activation (complement, cytokines)
- Progressive synaptic and neuritic injury
- Altered neuronal ionic homeostasis: oxidative injury
- Altered kinase/phosphatase activities ⇒tangles
- Widespread neuronal/neuritic dysfunction and cell death with transmitter deficits
- dementia
More details about Tau hypothesis (6)
- tau becomes hyperphosphorolated- lots of phosphates attach to it
- altered and increased kinase activity which add the phosphates to the tau
- the sketchy kinases also inhibit the proteins (phosphatase which is also an enzyme) that would take those phosphates off
- tau starts to stick together and create tangled clumps and are not abe to be cleared out fast enough in part due to aging
- microtubles disintegrate- organelles cannot get to their destinations, and cells will ultimately lose their structure.Tau are normally helpful microtubule helpers
- This is all occurring intercelluarly
Prion hypothesis (4)
- work by recruitment
- protein get misfolded
- misfolding spreads down the line
- hypothesis thought to be posible connection with development of AD.
What is Pick’s Disease? (5)
- Frontal and then temporal degeneration (dementia) occur. MRIs show marked loss of frontal cortex volume.
- Thought to be a problem of clearing misfolded proteins (ubiquitin/proteasome system)
- Loss of executive function occurs first, can overshadow memory disturbance.
- May look like bipolar disorder initially with poor choice making, or other psychiatric disorders, risk for misdiagnosis
- Neurons swell in the area of affected tissue, but no plaques or tangles are seen.
Treatment for Pick’s disease
There are no treatments to slow progression, but antidepressants and antipsychotics are used to treat symptoms.
Who are MaryBeth’s favorite brothers, aside from her own?
The Marx Brothers
