Autoantibodies Flashcards
What drives Abeta 42 inside the neurons?
Neuron binding Autoantibodies
How do neurons respond to autoantibody binding?
Surface-bound IgGs are internalized via endocytosis and degraded in lysosomes
What is the pathological significance of Autoantibody binding to neurons?
Abeta42 bound to neuronal cell surfaces is also internalized. Within the lysosomal compartment, Abeta42 self-assembles into fibrils that cannot be degraded. This drives chronic amyloid accumulation within neurons.
How does Autoantibody binding to neurons work?
Autoantibody binding induces endocytosis of IgG and amyloid and causes hypertrophy of the lysosomal compartment in pyramidal neurons of human AD brains
What determines the type of disease you have and the symptoms you experience?
The location of the BBB breakdown in the brain.
What determines the severity of the disease that you have?
The extent in which the BBB is damaged. The more damaged the BBB, the more severe the symptoms.
Darapladib -
Maintains/repairs blood-brain barrier integrity. It Blocks initiation and progression of multiple neurodegenerative diseases, but especially Alzheimer’s disease (Nagele-GSK Patent)
How is the BBB broken down?
There is endothelial cell contraction in the BBB, that causes the cells to pull away from eachother, opening a gap in the tight junction, breaching the BBB.
What are the effects of long term endothelial contraction of BBB cells?
Due to chronic inflammation of: AD, Parkinson’s, MS, atherosclerosis
What are the effects of short term endothelial contraction of BBB cells?
Due to irritating drugs and asthetics
hCMEC/D3 cells –
They are a human BBB cell line and Are the “gold standard” for the BBB
These cells express many common brain endothelial cell markers, TJ proteins, transporters, and receptors in culture
What is Histamine’s role in AD?
- Histamine triggers inflammatory response.
- increases permeability of capillaries to plasma components
- Histamine levels are reduced in elderly
- Alzheimer’s disease (AD) patients have 2x higher [histamine] in the blood, brain and cerebrospinal fluid.
- Cognitive impairment is increased in patients with higher histamine levels
- Hyperactivation of the histaminergic system
What is Histamine’s role in Artherosclerosis (heart disease)?
- It increases the permeability of capillaries to plasma components
- Histamine deficiency decreases atherosclerosis and inflammatory response
How does Histamine affect BBB?
Histamine causes BBB cell contraction and pulls on BBB tight junctions causing serrated or irregular margins blood vessel endothelial cells
