Ayaka Ohara

IR-2/11AP
February 6, 2018
Turn in Number: 11
Susan Levin
Regina Leckie
Memory Loss Could Be Due to Your Diet

“Every 66 seconds someone in the United States is diagnosed with Alzheimer’s disease;

Alzheimer’s disease kills more people every year than breast cancer and prostate cancer

combined” (Latest 1). Alzheimer’s disease is a form of dementia that causes severe problems

such as memory loss, behavioral and cognitive disorders. At the onset of this disease, one’s brain

and memory start to degenerate. This deterioration continues over the course of years or decades.

As there is currently no cure for Alzheimer’s disease and the prospect for one does not seem

imminent, it is vital that people take steps to prevent the disease before it occurs. Recent

literature suggests that the regulation of one’s diet and nutrition may prevent the

development of Alzheimer’s disease, as lowering the intake of saturated fats and increasing

the amount of antioxidants and omega-3 fatty acids may reduce inflammatory damage,

production of amyloid beta, and degeneration of the cell and cell membranes.

The repercussions of Alzheimer’s disease develop slowly over time, but as time passes,

severe cell death and shrinkage of brain tissue increases rapidly. Alzheimer’s is the most

prevalent kind of dementia, as it “accounts for 60 to 80 percent of dementia cases” (Alzheimer’s

disease 3). Dementia is a broad term for describing a set of symptoms that include impaired

memory and thinking. However, there are other diseases can cause dementia and similar

neurodegeneration, including Huntington’s disease and Parkinson’s disease. Alzheimer’s disease

is irreversible, while other causes of dementia, like vitamin deficiencies, are curable.

Although the symptoms of Alzheimer’s disease may vary widely among patients,

scientists have found key commonalities, such as amyloid plaques and tau tangles. Amyloid

plaques occur when proteins called amyloid beta accumulate in the brain, causing plaques to

form. Amyloid Precursor Protein (APP) binds to the cell membrane, where an enzyme cuts the
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protein into two fragments. Depending on the enzyme and where it is cut, there are two different

outcomes. In the normal case, the protein is cut in a way where the beta amyloid is not made, but

in the harmful case, the enzymes cut each end of the beta-amyloid, causing it to release and stick

to other peptides. These plaques reside outside nerve cells and disrupt signaling between the

cells. When this occurs in brain areas like the hippocampus, it results in memory loss.

Another signature of Alzheimer’s disease is an accumulation of tau proteins that create

tau tangles and reside inside the neuron. The nerve cell is usually held together by microtubules,

which help in the stabilization of the structure of the cell alongside tau proteins. Tau proteins

usually have a certain number of phosphate molecules attached to them, but in patients with

Alzheimer’s disease, an abnormally large amount of these molecules are present. When too

many phosphate molecules attach to the tau proteins, the proteins fall off the microtubule,

causing the microtubule to slowly unravel and the cell to lose its structure. The tau proteins then

bundle together and make tau tangles. The tau tangles choke the neurons, and disrupt the flow of

electric signals within the cell, resulting in cell death. Both amyloid beta and tau proteins are

found in abundance in the brains of patients with Alzheimer’s disease, and may be the most

prevalent factors that cause neuronal death and lead to the degradation of the brain.

The brain is essential in all functions in the body, from regulating one’s breathing and

heart rate, to coordinating one’s movements. In order for the brain to function at its best, it must

be supplied with essential nutrients. Nutrient dense foods contain minerals, antioxidants, and

vitamins, all of which have beneficial qualities to help nourish the brain. The opposite can be

said for processed or unhealthy foods, which have harmful components that may adversely affect

cognition.“‘[A] diet...[has] the potential to alter our brain health and mental function…. [and]
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changes in diet are a viable strategy for enhancing cognitive abilities, protecting the brain from

damage and counteracting the effects of aging’” (Wolpert 1).

There has been increasing evidence to suggest that diets consisting of certain foods and

nutrients have an important role in cognitive function and increase or decrease the risk of

developing Alzheimer’s disease. In order to sustain healthy neurons, the brain must receive

specific nutritional components. Lower intakes of “certain nutrients (i.e., DHA, B vitamins, and

antioxidants) have been linked to increasing risk for [Alzheimer’s disease], and a diet rich in the

aforementioned nutrients has shown to decrease the risk for [Alzheimer’s disease]” (Weiqian 3).

Different nutritional components could greatly affect the presence of amyloid plaques, tau

tangles, and phospholipid membranes of the neurons. Information and evidence surrounding the

nutritional components that affect Alzheimer’s disease are still controversial, but the three most

prevalent are saturated fats, omega-3 fatty acids, and antioxidants.

From a chemical standpoint, saturated fats are simply fat molecules that contain “no

double bonds, as they are saturated with hydrogen molecules” (Saturated Fat 1). They are found

in red meats and dairy and are present in high doses in Western diets. Saturated fats are

necessary in the body for energy, cell membranes, and signaling pathways, but an excessive

amount can lead to an increase of cholesterol levels, harming both the brain and the body.

Saturated fat diets most often contain cholesterol, an organic molecule that constitutes

cell membranes and other steroid compounds. There are two kinds of cholesterol: “High-density

Lipoprotein (HDL or “good” cholesterol), and Low-density Lipoprotein (LDL or “bad”

cholesterol)” (Granholm 2). In the conclusion of an experiment conducted by Ann-Charlotte

Granholm and her team of researchers, a diet high in saturated fat “gave rise to increased total

cholesterol, triglyceride and [(LDL)] serum levels….The LDL:HDL ratio was tripled” (3). In
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healthy brains, the amount of LDL and HDL are proportional, so a tripled ratio is considered

unhealthy and potentially harmful. HDL enters neurons via lipoprotein receptors located on the

neuronal membrane. Neurons need a specific amount of cholesterol (HDL) to function properly,

so a decrease in HDL or the dysfunction of lipoprotein receptors can cause cell death, thus

increasing the risk of Alzheimer’s disease. In addition, Lipoprotein receptor-related proteins are

involved in beta amyloid clearance in the brain. Lipoprotein receptors bind to amyloid beta either

directly or indirectly, preventing damage by beta amyloids and slowing brain degeneration. If the

receptor protein does not work properly, amyloid plaques will continue to accumulate in the

brain and further Alzheimer’s disease progression.

Conversely, higher levels of LDL can lead to more plaques and tangles. According to

Barnard, “higher total plasma cholesterol levels...may contribute to beta amyloid production and

aggregation of brain tissues” (2). As previously stated, cholesterol is essential in the cell

membrane. In a recent study where participants were fed saturated and unsaturated fat diets, the

diets “caused changes in the amounts of beta amyloid and ApoE...such that there was more beta-

amyloid present in those on the high saturated fat diet” (Rafii). This experiment shows a direct

link between increased saturated fat, higher amyloid, and an elevated risk of Alzheimer’s

disease. The increased saturated fat is one of the most prevalent factors in those with

Alzheimer’s disease, as many patients show an abundance of amyloid beta in the brain. Amyloid

beta can accumulate outside the neuron and create amyloid plaques, which disrupt the signals

between cells, causing memory loss. In addition to amyloid plaques, there is a high amount of

LDL in tau-bearing neurons, leading to the notion that a saturated fat diet leads to the

aggregation of tau tangles (Michikawa 4). A recent study by Rockwood and his colleagues

showed lipid-lowering agents linked to a lower risk of Alzheimer’s disease in 80 year olds. There
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have been multiple other observations that statin treatments, or lipid-lowering medications, lower

the risk of developing Alzheimer’s disease, leading to the inference that decreased total

cholesterol levels inhibits the production of amyloid beta.

In addition to amyloid beta and tau, other proteins, such as growth factors or Brain-

derived Neurotrophic Factors (BDNF), affect the functions of a cell. According to Gomez, “diets

that are rich in saturated fats appear to decrease levels of...(BDNF)...in the brain and lead to poor

neuronal performance” (Influence of Diet 3). BDNF genes stimulate the increased creation of

proteins related to the function and survival of nerve cells and are needed to introduce new,

healthy cells into the brain to replace old ones that have been damaged by plaques or tangles.

Without BDNFs, the brain will continue to degenerate and one’s brain function, including

memory, will become worse.

Omega-3 fatty acids are another nutritional factor prevalent in the development of

Alzheimer’s disease. Omega-3 fatty acids, polyunsaturated fatty acids with a double bond in the

carbon chain, are often found in salmon and walnuts. Although they are useful for numerous

functions in the body, such as eyesight and joint health, their specific benefits to brain health

include their ability to reduce plaques and increase BDNF and neuronal function.

Docosahexaenoic acid (DHA), a specific kind of omega-3 fatty acid, is the primary

structural component of the brain. It has been found through research that DHA “promotes

phospholipids’ synthesis, increases synaptic protein levels, enhance neurite outgrowth, and

increases dendritic spine density, all indicative of synapse formation” (Weiqian 3).

Phospholipids are an essential component of neuronal and synaptic membranes, as they make up

approximately a quarter of the dry weight in the brain. In the early stages of Alzheimer’s disease,

the cells in the hippocampus start to degenerate, which initiates the process of short term
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memory loss. Therefore, it is important that these membranes be maintained to ensure that nerve

cells work properly and carry out their normal functions, such as receptor activity and enzyme

function. With the cell membrane intact and working efficiently, the pathways in the brain will

be able to send signals to each other and ensure memory and thinking remains at its maximum

potential.

In addition, DHA increases acetylcholine levels in the brain. Data has shown that

“uridine can stimulate phospholipid synthesis without diminishing acetylcholine synthesis or

release in rat brain slices; and dietary supplementation with UMP (uridine monophosphate)

increases acetylcholine level” (Weiqian 3). Acetylcholine is a neurotransmitter, a chemical

released by nerve cells to send signals to other cells. Acetylcholine works in the parasympathetic

nervous system to put the body in a state of rest or regeneration and is important in learning and

memory formation. By acting as a neurotransmitter, it can quickly relay electrical signals in the

brain from the dendrites and axons of neighboring neurons. This communication of messages in

the brain diminishes in patients with Alzheimer’s disease, as synapses and neurons are

weakened. If one continues to consume DHA, they may be able to increase the acetylcholine in

their brain, and therefore keep the brain in better condition for preserving memory through

electric signals. Furthermore, DHA assists in nutrient transport and “in cellular signaling within

the cells,...DHA....act[s] as a lipid raft and transport nutrients within the cell on this lipid raft”

(Leckie). The cell needs specific nutrients in order to function properly in the brain. If it is

unable to receive the necessary nutrients, it could be more susceptible to damage and more

vulnerable to apoptosis, or cell death.

Furthermore, DHA may increase neuronal growth factors such as BDNF and Insulin-like

Growth Factors 1 (IGF1). Omega-3 fatty acids “activate energy-generating metabolic pathways
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that subsequently affect molecules such as..(BDNF) and...(IGF1)” (Gomez, Brain Foods 4).

BDNF and IGF1 are synaptic receptors that facilitate synaptic transmission and may be related to

long term memory and learning. In addition, BDNF results in cell proliferation by making new

cells in the brain and increasing neurogenesis, the development of nerve cells. In Alzheimer’s

disease, the neurons are susceptible to deterioration and death, so it is important that the brain

continues to make healthy cells and maintain the longevity of the current living neurons. DHA

enhances “cognitive abilities by...act[ing] through its effects on metabolism, as DHA

stimulates...mitochondrial function” (Gomez, Brain Foods 3). An increase of DHA in the body

can affect mitochondrial energy production, and the ATP produced by mitochondria activates

IGF1. IGF1, another growth factor, is located in liver and skeletal muscle and conveys

peripheral messages related to diet and exercise. The activation of IGF1 support nerve growth

and neurotransmitter synthesis in the brain.

Omega-3 fatty acids can cause reduction of amyloid beta and tau tangles. Amyloid

plaques are caused by “beta amyloid fragments that clump and stick to each other and create

more damage. DHA binds to the end of the fragments and prevents them from attaching to each

other” (Leckie). The plaques build up in the brain and prevent messages from being relayed

throughout the brain cells, causing a loss of memory. With DHA, the ability for plaques to

accumulate diminishes, preventing severe loss of memory.

Antioxidants are the final nutritional factor that has shown to be beneficial for the

prevention of Alzheimer’s disease. Chemical reactions constantly occur in the body. Some result

in the combination of oxygen with another molecule, creating free “radicals.” Free radicals “are

atoms or molecules that are highly reactive with other cellular structures” (About 3) and are a

natural byproduct of immune system responses or metabolic processes. An abundance of free

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radicals can lead to oxidative damage, which occurs when there is “an imbalance between

antioxidants and reactive oxygen species within a cell” (Grundman 1). The oxidative damage

means that electrons are taken away from the cells, which severely undermines specific parts in a

cell, such as the DNA or the cell membranes. With the electrons taken away, the structure of the

cell starts to fall apart and the cell could potentially die. Antioxidants help to prevent this damage

by eliminating the free radicals.

Alzheimer’s disease patients tend to have lower antioxidant levels, which leads many

scientists to believe that the lack of antioxidants plays a critical part in the escalation of free

radicals and oxidative damage, leading to cell death and the development of Alzheimer’s disease.

According to an experiment conducted by Von Arman, “antioxidant users had a 29% lower risk

of experience cognitive decline” (4). The antioxidants that the subjects were given included

Vitamin A, C, and E. An antioxidant-rich diet, and other foods with antioxidant characteristics

such as green tea, caffeine, and plum juice have been shown to restrict amyloid beta production

and slow down cognitive impairment. An abundance of amyloid beta can have detrimental

effects on the brain and lead to extreme memory loss.

Vitamin B decreases amount of homocysteine, which is a pro-inflammatory marker that

produces an immune response and damages the cell. There are many factors that can affect the

speed of brain degeneration, one of which is high levels of homocysteine, an amino acid that is

situated in the blood. There have been multiple studies showing the link of B Vitamins to

Alzheimer’s Disease and how increasing levels of homocysteine in the blood can lead to a raised

risk of Alzheimer’s Disease, as “Folate, Vitamin B6, and B12 act as cofactors for the

methylation of homocysteine.” (Von Arman 2). An increased amount of homocysteine in the

blood can be extremely detrimental to both the brain and body by triggering an immune response
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that kills cells. However, the amount of homocysteine may decrease through intakes of Vitamin

B. According to a recent experiment,“treatment with vitamin B tablets had notable effects on the

levels of homocysteine in the blood, reducing it by 22.5 percent” (Alzheimer’s and

Homocysteine 1). Furthermore, homocysteine is found to be related to strokes, as “25% of

dementia cases are attributed to stroke” (Morris, Homocysteine 3). Homocysteine is also known

to be an independent risk factor for a stroke and Alzheimer’s Disease is known to co-occur with

it.

Vitamin E helps eliminate free radicals and prevent oxidative stress. Beta amyloid is

found in abundance in the brains of Alzheimer disease patients, “is toxic in neuronal cell cultures

through a mechanism involving free radicals” (Grundman 2). The accumulation of free radicals

can be dangerous in the brain, as they destroy cell membranes, an integral part of cells that helps

to maintain their structures. Without a solid cell membrane, the cell is more vulnerable to

degeneration and creation of tau tangles and amyloid plaques. Vitamin E functions as “an

antioxidant, reducing free radicals in the brain, which would otherwise impede optimal function

of neurons” (Gomez, Diet 4). In addition, the free radical formation in the brain causes cross-

linking, or clustering, in tau proteins and amyloid beta. Antioxidants can prevent this by pulling

the amyloid beta away from each other and preventing them from clumping and untangling the

tau proteins.

Alzheimer’s disease is a prevalent disease that is affecting millions of lives each year. In

30 years, almost 16 million Americans will be diagnosed with Alzheimer’s disease (Latest).

Because there is no cure for this disease, it is important to raise more awareness about prevention

and more funding for research. With the current information available, three nutritional strategies

for prevention have emerged as the most prominent: a decrease in saturated fats and an increase

in omega-3 fatty acids and antioxidants. Saturated fats can increase levels of cholesterol, which
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causes more amyloid plaques to accumulate in the brain. In addition, it decreases BDNF and

prevents the brain from creating new, healthier neurons. Omega-3 fatty acids help in

phospholipid synthesis and synapse formation, ensuring nerve cells properly carry messages

throughout the brain, stopping deterioration of memory and thinking. Finally, antioxidants

decrease the amount of homocysteine, an amino acid that causes an immune response for

Vitamin B, and the reduction of oxidative stress and free radicals for Vitamin E. Following these

health guidelines will remarkably decrease one’s risk of developing Alzheimer’s disease. As

treatments and cures are currently unavailable, prevention through diet and nutrition is the best

method to prevent degeneration of the brain and diagnosis of Alzheimer’ disease.