The End of Alzheimer's, Dale E. Bredesen
"What the research from my laboratory colleagues and me adds up to is this: No one should die from Alzheimer's disease."
"And the reason for that is one fundamental discovery: Alzheimer's "disease" is not the result of the brain doing something it isn't supposed to do, the way cancer is the result of cells proliferating out of control or heart disease is the result of blood vessels getting clogged with atheroscelerotic plaque. Alzheimer's arises from an intrinsic and healthy downsizing program for your brain's extensive synaptic network."
"Alzheimer's is different. As I explain in detail in chapter 4, one of the key discoveries to come out of my lab is that Alzheimer's arises when the brain responds as it should to certain threats. Why would evolution give us a brain that works like this? Because in most cases this response to outside threats succeeds; the brain beats back the threat and goes on functioning just fine. The problem comes when those threats are chronic, multiple, unrelenting, and intense. In this situation, the defenses that the brain mounts are also chronic, multiple, unrelenting, and intense--so much so that these protective mechanisms cross the line into causing harm. Specifically, Alzheimer's disease is what happens when the brain tries to protect itself from three metabolic and toxic threats:
Inflammation (from infection, diet, or other causes)
Decline and shortage of supportive nutrients, hormones, and other brain-supporting molecules
Toxic substances such as metals or biotoxins (poisons produced by microbes such as molds)"
"Cellular suicide is a normal process when it occurs at the right place and time. For example, in the time it takes to count to two, a million of your white blood cells have committed suicide! And they have been replaced by a million new white blood cells. Such programmed cell death is critical for many of our bodily functions, and we would not be alive without it. Without cell suicide, we would have webbed fingers (since we would not lose the tissue between them), a brain that grows right out of the skull, and rampant cancers (because cells that become malignant would survive rather than commit suicide, as many actually do), along with many other problems. So cell suicide is crucial for life."
"Why did we not try to test a single drug? By this time, we had a good sense of how many "holes" would have to be patched--how many molecules the brain needed more of or less, how many brain processes needed to be revved up or quieted down--in order to treat Alzheimer's disease: at least thirty-six. However, just to be sure, our 2011 proposed trial included a group that was treated with tropisetron alone, so that we could compare this with the program, as well as a combination of the two."
"Today, most people carry two copies of ApoE3. This gives them a genetic risk of Alzheimer's of about 9 percent. But 25 percent of Americans, about 75 million, carry a single copy of ApoE4; they have a risk of Alzheimer's disease of about 30 percent. And 7 million carry two copies of ApoE4, pushing their risk well above 50 percent. That is, it is more likely than not that people who inherited an ApoE4 from both parents will develop Alzheimer's, and this is often, thought not always, the inflammatory subtype."
"There is direct mechanistic link between inflammation and Alzheimer's disease. If you've ever called the police, then you have depended on them to distinguish the "good guys" from the "bad guys," capture the latter, and then return to the station. Imagine, however, that the police never leave your neighborhood--that you lived in a police state, with ongoing shooting, damage, and death, and indiscriminant injury to both good and bad guys. This is just what is happening to most of us: our immune system--our internal police force--never stands down completely, and the resulting chronic (albeit mild) inflammation leads to cardiovascular disease, cancer, arthritis, accelerated aging--and Alzheimer's disease. The evidence that inflammation contributes to Alzheimer's disease is overwhelming. Besides being overactive in general, the chronically activated immune system sometimes attacks the body's own tissues."
"Stress, which seems to be everywhere in our hyperconnected, über-productive, constantly competitive world, is one of the most important contributors to cognitive decline. Short periods of stress that you get over are less of a problem than the chronic unresolved stress that so many of us experience."
"For centuries, we humans typically died from acute infections such as bacterial pneumonia, and the great biomedical success of the twentieth century was to develop antibiotics that treat them and public health policies that prevent them. As a result, most of us now die from chronic, complex illnesses such as cancer, cardiovascular disease, and neurodegenerative disorders. Unfortunately, we tried to solve the problem of chronic illness in the same way we solved the problem of acute illness: with a single pill, monotherapy. This is like using your checkers strategy in a chess match."