Death of Neurons and BBB Flashcards
What physiological process in neurons causes the loss of memory and cognition?
Amyloid (Abeta42) deposits in neurons; neurons retract their axons and dendrites and lose synaptic connections with each other
Describe the processes and enzymes used that causes the formation of Amyloid plaques/accumulation.
- The Amyloid Precursor Protein (APP) gets cleaved once by Beta Secretase.
- Gamma Secretase - cleaves APP a 2nd time resulting in Amyloid Beta 42 protein
- AB42 accumulates in neurons
What is the most modern Model that attempts to understand and treat AD?
New Model:
Neurons accumulate excessive Abeta42 intracellularly.
Amyloid overburdened neurons die by lysis and release their fibrillized amyloid content to form plaques.
What are some important proteins associated w/ Amyloid Plaques?
Ubiquition
Cathepsin - lysosomal aspartyl protease (degrades proteins)
Tau
Neurofibrillary Tangles -aggregates of hyperphosphorylated tau protein
Amyloid Plaques are also nicknamed?
Grave markers
The size of the Amyloid plaque correlates w/ the size of what?
Size of neurons
What is the first thing that we see when a neuron begins accumulating Amyloid?
A retraction of the dendrites (loss of synapses), but the neuron isn’t dead yet. It takes many years for the neurons to die.
What do scientist believe is the key to treating AD? and Why?
Treating the BBB, because more plasma leaks out of damaged Blood vessels, and the plasma carries tau protein.
What is the major structural component of the BBB?
The tight junctions
What is the BBB?
- Structural and functional barrier located in the walls of blood vessels
- Essential for normal functioning of neurons in the CNS
- Restricts and regulates the passage of molecules in and out of the brain - maintains brain homeostasis.
How is the BBB formed?
• Formed primarily by brain vascular endothelial cells (BVECs) - supported by astrocyte end feet and pericytes
What substance/structure forms when the BBB is defective and the Plasma components (including Abeta42) leak into the brain?
They form vascular leak clouds
What causes the BBB to leak?
Aging Infections Diabetes High Cholesterol Smoking Traumatic brain injury *High BP *Vascular inflammation *Artherosclerosis Anesthesia
List Some Anesthesias that poke holes in the BBB.
Isoflurane and Sevoflurane
How do Anesthesias damage the BBB?
They smooth out the surface of the membranes and poke holes in the BBB.
