The Clue to Why Low Fat Diet and Statins may Cause Alzheimer’s
abstract
Alzheimer’s disease is a devastating disease, and its incidence has increased significantly in the United States. Fortunately, a lot of research funds are currently being spent to try to understand what causes Alzheimer’s disease. ApoE-4 is a specific allele of apolipoprotein apoE and is a known risk factor. Since apoE plays a key role in the transportation of cholesterol and fat to the brain, it can be assumed that insufficient fat and cholesterol in the brain play a key role in the disease process. In a recent major study, compared with patients without Alzheimer’s disease, the concentration of free fatty acids in the cerebrospinal fluid of patients with Alzheimer’s disease was only 1/6. At the same time, cholesterol is ubiquitous in the brain, and it plays a key role in nerve transport in synapses and maintaining the health of myelin-coated nerve fibers. This has become very clear. It has been found that a very high-fat (ketogenic) diet can improve the cognitive abilities of patients with Alzheimer’s disease. These and other observations described below led me to conclude that a low-fat diet and statin treatment increase the susceptibility to Alzheimer’s disease.
Introduction
Alzheimer’s disease is a devastating disease that gradually eliminated the mind in decades. It starts with a strange memory gap and then steadily damages your life. This is the only option. With severe Alzheimer’s disease, you can easily walk, get lost, and may not even recognize your own daughter. Alzheimer’s disease was a little-known disease before 1960, but today it has the potential to completely destroy the American health system.
Currently, more than 5 million people in the United States suffer from Alzheimer’s disease. On average, the medical expenses of Alzheimer’s disease patients over 65 years old are three times that of Alzheimer’s disease. Even more shocking is that the incidence of Alzheimer’s disease is rising. Dr. Murray Waldman studied epidemiological data comparing Alzheimer’s disease and femoral fractures, looking back over the past fifty years [52]. Shockingly, he found that although the incidence of femoral fractures (another condition that usually increases with age) only increased at a linear rate, the increase in the incidence of Alzheimer’s disease increased exponentially, from 1960 to The prevalence of Alzheimer’s disease during 2010 [15]. Between 2000 and 2006, the number of deaths from Alzheimer’s disease in the United States increased by 47%. In contrast, combined deaths from heart disease, breast cancer, prostate cancer, and stroke fell by 11%. This increase far exceeds the longevity of people’s lives: for people 85 years and older, the percentage of deaths from Alzheimer’s disease rose by 30% between 2000 and 2005 [2]. In the end, it is likely that these estimates are underestimated, because many people with Alzheimer’s disease end up dying of something else. You may have a close friend or relative who has Alzheimer’s disease.
Certain things in our current lives are increasing the likelihood that we will succumb to Alzheimer’s disease. My belief is that the two main contributors are our current obsession with low-fat diets, coupled with the increasing use of statins. I have argued elsewhere that low-fat diets may be a major factor in the alarming increase in childhood autism and infant depression. I also think that the obesity epidemic and related metabolic syndrome can be traced back to excessive low-fat diets. As I said here, statins may help many serious health problems besides Alzheimer’s, such as sepsis, heart failure, fetal damage and cancer. I believe that the trend in the future will only get worse, unless we drastically change our current “healthy life” view.
The ideas developed in this article are the result of extensive online research I conducted to understand the development of Alzheimer’s disease. Fortunately, a lot of research funds are currently being spent on Alzheimer’s disease, but the clear cause is still elusive. However, many exciting clues are fresh, and these puzzles are beginning to integrate themselves into a coherent story. Researchers have only recently discovered that fat and cholesterol are severely deficient in the Alzheimer’s brain. Facts have proved that fat and cholesterol are important nutrients in the brain. The brain contains only 2% of body mass, but 25% of total cholesterol. Cholesterol is essential in transmitting nerve signals and fighting infection.
A key part of the puzzle is to place people on the genetic marker of Alzheimer’s disease called “apoE-4.” ApoE plays a central role in the transportation of fat and cholesterol. There are currently five known different variants of apoE (appropriately called “alleles”), and the ones labeled “2”, “3” and “4” are the most common. ApoE-2 has been shown to provide some protection against Alzheimer’s disease; apoE-3 is the most common “default” allele, apoE-4 is present in 13-15% of the population, and is related to Alzheimer’s Alleles associated with increased risk of silent disease. People with apoE-4 alleles inherited from their mothers and fathers have a twenty-fold increase in the likelihood of developing Alzheimer’s disease. However, only about 5% of Alzheimer’s patients actually have the apoE-4 allele, so obviously there are others for the rest. However, understanding the many effects of apoE in the body is a key step that led to my low-fat/statin theory.
2. Background: Brain Biology 101
Although I tried to write this article in a non-expert way, it would be helpful to be familiar with the basic knowledge of brain structure and the role of different cell types in the brain.
At the simplest level, the brain can be described as consisting of two main components: gray matter and white matter. Gray matter includes the body of neurons, including the nucleus, and white matter contains countless “wires” that connect each neuron to every other neuron that communicates with it. Wires are called “axons,” and they can be quite long, such as neurons connected to the frontal cortex (above the eyes) and other neurons deep in the brain related to memory and movement. In the following discussion, axons will appear prominently because they are coated with a fatty substance called myelin, and this insulating layer is known to be defective in Alzheimer’s disease. Neurons pick up signals transmitted through axons, called synapses. The information here needs to be sent from one neuron to another, and various neurotransmitters such as dopamine and GABA can excite or inhibit signal strength. In a single axon, a neuron usually has several shorter nerve fibers called dendrites, whose job is to receive input signals from different sources. At a given point in time, the signals received from multiple sources are integrated in the cell body, and it is determined whether the cumulative signal strength is higher than the threshold. In this case, the neuron responds by triggering a series of electrical impulses, and then The axon spreads to a destination that may be far away.
In addition to neurons, the brain also contains a large number of “helper cells” called glial cells, which are involved in the maintenance and feeding of neurons. The three main types of glial cells that we will discuss later will play a role: microglial cells, astrocytes and oligodendrocytes. Microglia are equivalent to white blood cells in the rest of the body. They are concerned about the fight against infectious agents such as bacteria and viruses, and they also monitor the health of neurons and make life-and-death decisions: to program a specific neuron to undergo apoptosis (intentional self-destruction) or to be killed by an organism. Infection, this creature is too dangerous to allow prosperity to happen.
Astrocytes are prominent in the following story. They are matched with neurons and are responsible for ensuring an adequate supply of nutrients. Studies on the culture of neurons in the central nervous system of rodents have shown that neurons rely on astrocytes to supply cholesterol [40]. Neurons need cholesterol in both synapses [50] and myelin [45] in order to successfully transmit signals and are the first line of defense against microbes invading. Cholesterol is so important to the brain because astrocytes can synthesize from alkaline components, which are not found in most cell types. They also provide fatty acids for neurons, which can absorb short-chain fatty acids and combine them to form long-chain fatty acids that are particularly prominent in the brain [7] [24] [36] and then deliver them to neighboring nerves Yuan and cerebrospinal fluid.
The third type of glial cell is the oligodendrocyte. These cells are specifically used to ensure that the myelin sheath is healthy. Low-molecular-weight nuclear cells synthesize special sulfur-containing fatty acids from other fatty acids supplied by cerebrospinal fluid, called sulfatides [9]. Sulfates have been shown to be necessary for maintaining myelin. Children born with defects in the ability to metabolize sulfates suffer from progressive demyelination, rapid loss of motor and cognitive functions, leading to early death before the age of 5 years [29]. The consumption of sulfa drugs is a well-known sign of Alzheimer’s disease, even in the early stages of it has been considered cognitive decline [18]. ApoE has been shown to play a vital role in maintaining sulfatides [19]. Throughout human life, the myelin sheath must be maintained and repaired continuously. This is something that researchers have only begun to appreciate, but two related properties of Alzheimer’s disease are poor quality myelin sheath, and the concentration of fatty acids and cholesterol in the cerebrospinal fluid drops sharply [38].
3. Cholesterol and lipid management
In addition to some knowledge about the brain, you also need to know something about the process of delivering fat and cholesterol to all tissues in the body, paying special attention to the brain. Most cell types can use fat or glucose (simple sugar from carbohydrates) as fuel to meet their energy needs. However, the brain is a huge exception to this rule. All cells in the brain, neurons and glial cells cannot use fat as fuel. This may be because fat is too precious to the brain. The myelin sheath needs a constant supply of high-quality fat to insulate and protect the enclosed axons. Since the brain needs its fat for long-term survival, it is vital to protect them from oxidation (exposure to oxygen) and invasive microorganisms.
Fat comes in various shapes and sizes. One dimension is saturation, which involves the double bonds they have. There are no saturated fats, only one monounsaturated fat, and two or more polyunsaturated fats. Oxygen destroys double bonds and oxidizes fat, which is problematic for the brain. Therefore, polyunsaturated fats are most vulnerable to oxygen damage due to multiple double bonds.
Fat is digested in the intestine and released into the blood in the form of larger spheres with protective protein shells called chylomicrons. Chloromicrons can directly provide fuel to many cell types, but they can also be sent to the liver, where the fat contained in it is sorted out and redistributed into smaller particles, which also contain large amounts of cholesterol. These particles are called “lipoproteins” (hereinafter referred to as LPP) because they contain protein in the shell and lipid (fat) inside. If you measure cholesterol, you may have heard of LDL (low density LPP) and HDL (high density LPP). If you think that these are two different kinds of cholesterol, you will be mistaken for it. They are just two different types of cholesterol and fat containers, which play different roles in the body. There are actually several other LPPs, such as VLDL (very low) and IDL (intermediate), as shown in the attached picture. VLDL, IDL, LDL, HDL In this article, I will refer to these collectively as XDL. As if this is not confusing, there is another unique XDL that can only be found in the cerebrospinal fluid, which provides the nutritional needs of the brain and nervous system. This seems to have no name, but I call it “B-HDL” because it is like HDL, “B” is “brain[13]”
An important thing about all XDLs is that they contain significantly different compositions, and each combination is targeted (programmed) to a specific tissue. A group of proteins called “apolipoproteins”, or equivalent to “apoproteins” (“apo” for short), powerfully control who the chylomicron structure gets what can be seen from the schematic diagram of the chylomicron shown on the right, it A rainbow of different apo can be included for each possible application. But XDL is more specific. HDL contains “A”, LDL containing “B”, VLDL containing “B” and “C”, and IDL containing only “E”. Apolipoprotein has special binding properties, allowing lipid content to be transported through the cell membrane, allowing cells to enter the fat and cholesterol contained inside the fat.
In the context of this article, the only apo we care about is apoE. ApoE is very important to our story because of its known connection with Alzheimer’s disease. ApoE is a protein, that is, an amino acid sequence, and its specific composition is determined by the corresponding DNA sequence on the protein-coding gene. Certain changes in the DNA code result in defects in the ability of transcribed proteins to perform their biological functions. ApoE-4, the allele associated with an increased risk of Alzheimer’s disease, may not perform the task as efficiently as other alleles. By understanding the role of apoE, we can better infer how the consequences of this approach affect the brain, and then observe through experiments whether the characteristics of the Alzheimer’s brain are consistent with the role of apoE.
Strong clues about the role of apoE can be inferred from where it was discovered. As mentioned above, it is the only apolipoprotein of B-HDL in cerebrospinal fluid and IDL in serum. Only selected cell types can synthesize it, the two most important of which are our astrocytes in the liver and brain. Therefore, astrocytes provide the connection between blood and cerebrospinal fluid. They can cause lipids and cholesterol on the blood-brain barrier through the special key of apoE.
It turns out that although apoE is not found in LDL, it binds to LDL, which means that astrocytes can release the key to LDL in the same way that IDL can be obtained, so cholesterol and fatty acid content as long as apoE works properly , Astrocytes can also use LDL. Astrocytes remodel and repackage lipids and release them into the cerebrospinal fluid as B-HDL and simple free fatty acids, which can be taken up by all parts of the brain and nervous system [13].
One of the important remodeling steps is to convert fat into a type that is more attractive to the brain. To understand this process, you need to understand another dimension of fats, apart from their saturation, which is their total length. Fat has a chain of connected carbon atoms as its spine, and the total number of carbons in a particular fat is expressed as short, medium or long. When the component fat is long, the brain works best, and astrocytes can accept short-chain fat and reorganize to form longer chain fat [24].
The final size of the functional fat is that the first double bond is located in the polyunsaturated fat, which distinguishes omega-3 from omega-6 fat (position 3; position 6). Omega-3 fats are very common in the brain. Certain omega-3 and omega-6 fats are essential fatty acids,