Microglia Cells; Immune Response
(Episode 568) 21:34 – Dead cells in the brain lead to microglia cells rushing from the rest of the body towards the blood brain barrier attempting to close of leaks. This is an immune response that, as we shall see, leads to many problems.
(Episode 568) 22:08 – The microglia also try and ‘eat up’ cellular debris that remains from the cells dying en masse. This clean up process causes inflammation in the brain. Within hours of an sever injury, the brain begins to accumulate amyloid beta plaques as a result of the microglia response.
Amyloid Beta Plaque
(Episode 568) 23:23 – Amyloid beta plaque in detail. Amyloid beta plaques are a major pathology associated with alzheimer’s. These plaques form outside of neurons and this disrupts glucose metabolism and creates even more reactive oxygen species (a vicious cycle). On top of that, the microglia cells try and clean the plaque, this causes more plaque. This does not have to come from brain trauma, this cycle can become a huge problem after 7 or 8 decades of just being alive.
25:28 – Tao protein. This protein (found inside the neuron) transports material around the brain and is essential for healthy brain function. The immune response activated after a traumatic brain injury or the increased microglia cell activity as a result of aging, causes these tao proteins to aggregate and it can no long transport its cargo. The train became derailed. Synapses start to die and thus these cells have no purpose and die – this is brain atrophy. We can see this in cases of severe brain injury and in alzheimer’s patients.
(Episode 568) 27:19 – The accumulation of amyloid beta plaque and the tao protein tangles are two prominent features of alzheimer’s. They cause inflammation and reactive oxygen species to be generated and lead to a cycle that won’t stop.
Polymorphisms; Alzheimer’s; APOE4
(Episode 568) 35:06 – Dr. Patrick covers polymorphisms and the genetic predisposition some people have towards neurodegenerative diseases. A polymorphism is a slight change in the sequence of a gene and this slight change alters the function of that gene somewhat. From an evolutionary standpoint, polymorphisms are are changes that are selected unlike mutations which are random. Some polymorphisms seem counterproductive but Dr. Patrick believes that there could be a reason they exist and therefore there may be some benefit that we don’t understand. ApoE3 is a polymorphism in a gene responsible for transport and repair and the majority of the population has this variation. People with the ApoE4 variation (25% of the population) have a 2-3 fold increase risk of alzheimer’s. People with the ApoE4 variation and a traumatic brain injury suffer a 10 fold increase risk of getting alzheimer’s.
(Episode 568) 40:10 – ApoE4 in detail. With this variation of the gene, you cannot repair damage as easily. One solution is to literally bypass the amyloid beta plaque obstruction in between neurons via neural outgrowth. Neural outgrowth is the growing of neurons to reconnect a connection obstructed by the plaque. Transporting essential fats and material is needed in this outgrowth process and ApoE4 makes it more difficult to transport material. Furthermore, in times of repair, the body will request activity from the genes responsible for repair. If the ApoE4 is the variation that is being called upon, then the negative effects are exacerbated because there are problems with protein aggregation that comes from the ApoE4 variant (another instance of a vicious cycle). You can test if you have this by doing 23andMe.
Decreasing Alzheimer’s Risk
(Episode 568) 45:34 – How sleep removes amyloid beta plaque. The brain swells because cerebral spinal fluid is being pushed up into the brain and this process pushes out plaque (and other trash) in between neurons. People with ApoE4 really need to make sure they get enough sleep to compensate for the gene variant’s poor performance in cleaning the brain.
(Episode 568) 47:38 – Nutrition’s role in alleviating the problem. Data shows that obese, type II diabetic, and insulin resistant individuals also have an increased risk for alzheimer’s. This suggests something about not having the right diet can lead to this increase in risk. Figuring out exactly what is responsible in diet is very complicated, but generally there seems to be a link.