Alzheimer's

- A scan can be completed in approximately one second without dilation of the pupil and multiple scans with different targets and angles can be taken in less than five minutes; results are immediate. It is also inexpensive, especially in comparison to current diagnostics and amyloid imaging in the brain. - The test is also very safe, there is not toxicity risks and it's easy. Obviously it's much better if blood doesn't have to be drawn and no spinal taps are needed.

- At Harvard University, they have found the ability to isolate Alzheimer's markers via stem cells in vitro. This allows scientists to test drugs limitlessly without the consequences of doing it in vivo and killing the organism. It is also more relatable since human stem cells are being used rather than being tested inside mice. It is said that through this method and with the right compounds, plaque formation can actually be prevented or reduced. Eventually this model could actually be used to research similar diseases such as Huntington's and Parkinson's.

- Critical research has helped identify the key steps into the formation of how brain abnormalities occur in the more common version of the disease (late-onset AD). Research also helps explain why the disease develops in people at various ages

- By further examining of the disease, scientists monitor how it develops before symptoms occur. They tend to study families with long histories of reoccurring early-onset familial AD and test amyloid-clearing drugs in symptom free volunteers at high risk of developing FAD.

Economic Concerns - The estimated global cost of dementia was estimated at $604 billion in 2010. - AD is diagnosed using very expensive and lengthy processes to eliminate other probable causes. - It nearly takes two years to be evaluated and another to make a clear and exact diagnosis.

- By the time a diagnosis is made, the patient will have typically deteriorated by 40-50% since the brain has already a huge buildup of plaques and tangles before any symptoms show. Since Alzheimer's is a progressive, irreversible disease, only preventative measures can be taken to ease the development and the brain damage cannot be reversed. This has been determined through clinical trials that only intervention and early treatment can only slow down and reverse only early progression of the disease.

- Environmental factors that can influence the development of AD or any disease: - Food - Western type diets - Saturated fats and cholesterol; saturated fat in many controlled animal dietary experiments has been shown to impair cognition in comparison to high poly- or mono-unsaturated fats of which no impairment occurred. - Water supply

- Education - Socioeconomic status (social and economic position in relation to others, which is based on income, education, and occupation). Usually associated with many other factors like poor nutrition, exposure to pollutants, etc. Poor education, and low socioeconomic status could potential increase the odds of AD by threefold in comparison to high education and socioeconomic status.

- Sanitation facilities - Climate - Physical, social, and mental inactivity - Alcohol consumption - Smoking

- High chemical exposure to: lead, pesticides, aluminum salts used in drinking water, colourants for snacks and desserts, and make baking goods rise ( and found most in varieties of baking powder, pancake/waffle mixes, frozen products, ready to eat pancakes), copper, iron, zinc, PCBs (industrial chemicals such as paint additives, lubricants, and insulators)

- APOE ε3, which is the most common allele, as far as researchers know plays a neutral role in the development, neither increasing nor decreasing. - APOE ε4 is the risk allele that increases the risk and is associated with earlier development. The more APOE ε4 a person has, the more at risk he/she is; a person can have zero, one, or two.

- Inheriting this allele does not mean that the person will develop the disease for sure, just like any other risk gene. Whole genome sequencing of the complete DNA sequence can help determine the alleles that are involved in each case of AD but will not determine whether each person will or will not develop

Memantine is a receptor antagonist which regulates the activity of glutamate, an important neurotransmitter that is involved in memory and learning and allows neurons to intake and release calcium. When cells are damaged during Alzheimer's, there is an excess amount of glutamate released, which thus leads to chronic overexposure of calcium and speeds up the damage of neurons.

- Reaction to these medications vary across every patient, some benefit greatly and some very little or not at all. - These drugs help by masking symptoms but do not treat the underlying cause of AD.

The only thing that genetic screening does for someone is demonstrates the chances of acquiring the disease and if one is high at risk, this signals scientists to keep a close watch at early brain changes which can be done in clinical trials

- Right now, genetic testing can be down on embryos that are conceived in vitro fertilization. The parents can choose which embryo out of the bunch they prefer, usually without inherited diseases like Alzheimer's passed by the parents and then they can have it implanted into the mother. There's not much the child can really be picky on since if the parents did not pick him/her, then that child would not be alive.

- These two proteins that build up in the brain leads to nerve cells death and tissue loss all throughout the brain. Eventually, the brain shrinks dramatically and nearly all of its functions are destroyed or compromised.

- The cortex shrivels up, damaging the areas of the brain that allow us to think, to plan, and to remember. The hippocampus shrivels dramatically as well, the area that allows the formation of new memories. The ventricles (the fluid-filled spaces) actually grow larger as the rest of the brain shrinks. - Video of how the brain is affected and in which order

- The amyloid plaques form when protein pieces called beta-amyloid peptides clump together and collect outside nerve cells. They disrupt cell-to-cell signaling in neurons. The communication breakdowns is the reason behind patients suffering from progressive memory loss, confusion, and difficult doing easy day-to-day tasks.

- The neurofibrillary tangles form when the tau protein becomes hyperphosphorylated and become defective, no longer stabilizing the microtubules properly. This destroys fundamental cell transportation systems and nutrients can no longer make it to the cells, and thus they eventually die.

Treatment - There are five FDA (the US Food and Drug Administration) approved Alzheimer's medications. Drug Name Brand Name Approved for: Donepezil Aricept All stages Galantamine Razadyne Mild to moderate Memantine Namenda Moderate to severe Rivastigmine Exelon All stages Donepezil&memantine Namzaric Moderate to severe

- There are two ways these drugs work: - Donepezil, galantamine, and rivastigmine are cholinesterase inhibitors. They work by slowing the breakdown of a key neurotransmitter that increases neurotic AD plaques.

To be able to treat a patient, s/he must be diagnosed. Generally diagnosis takes a very long time to do (I will talk about this later) but a new method is being fabricated for cheaper and easier diagnostic.

- There has been many connections established between the eye and the brain but most recently the discovery of Aβ, a component of the AD plaque that forms in the brain, which grows in the lens of the eye. It is parallel to the plaque growth in the brain.

In some people, plaque growth could be building for up to 30 years in the brain before the person starts developing symptoms. Scientists are aiming at making this diagnostic technique a basic medical test for everyone once it is perfected.

- What happens though? - The day before the procedure, an ophthalmic ointment that contains amyloid-binding ligand is applied to the inner eyelid. A low-power laser is used to scan the lens of the eye. This process makes the amyloid in the eye fluorescent and data is collected to determine how much is in the eye.

21: signals the formation of abnormal amyloid precursor proteins (APP), a primary driver for Alzheimer's disease-related pathogenesis. This means that there are increases in neurofibrillary tangles forming, synapse (which is a junction between nerve cells that allow impulses to pass from an axon terminal to a neuron) can be signaled to stop, and thus increases neuronal cell death.

14: signals the formation of abnormal presenilin 1 1: signals the formation of abnormal presenilin 2 - Each of the presenilin plays a role in the breakdown of APP which generates amyloid plaque - The function of APP has not been discovered yet

- This in vitro method could potentially aid researchers identify compounds that could advance the development of the cure for AD because not only is it ten times as fast but it is also ten times less expensive in comparison to animal methodology and other techniques, which is another hurdle to deal with when researching Alzheimer's.

AD is becoming very important because it is affecting more and more people and it is also becoming very expensive to treat and care for. Some researchers are actually considering that it's becoming a bit of an epidemic seeing as there are 36 million people affected worldwide and it could potentially bankrupt the healthcare system.

A common genetic linkage to common late-onset Alzheimer's disease was found on chromosome 19. On this chromosome, there is a common polymorphism (or rather genetic variation within a population) in the gene that codes for apolipoprotein E (APOE) in the same region of the gene associated with increased risk of late-onset AD.

About 15% of people carry this gene risk, but even with that percentage, carrying one or two copies of the polymorphism is neither necessary nor sufficient to actually ensure one develops the disease. This applies to all gene risks. - APOE ε2 is one gene factor that can provide some protection against Alzheimer's disease. This factor seems to help prevent the disease altogether or postpones the development of it.

Gene Risks - Between the UK, Germany, and the United States, they have collected the largest sample of DNA from individuals with Alzheimer's (over 4000 samples). Through this collection they have discovered 21 risk genes that link to Alzheimer's.

Early-onset AD which occurs in people age 30-60, is only 5% of people with Alzheimer's. Early-onset Alzheimer's is usually inherited in one of three genes (point mutations on chromosomes 21, 14, and 1), which is also known as early-onset familial Alzheimer's or FAD. Without the genetic factors, reasons to describe how early-onset are unknown so far. It seems to appear almost without any specific cause but rather a combination of factors from the environment play a role.

Before, if they had chosen the healthy child, it would've been you, otherwise you would not exist. Tomorrow, children realize their parents could've chosen a different version of them just as easily. - Soon enough, genetic screening will be a parental responsibility and there is definitely the potential for a superior race for those who have the means without restrictions or limitations on CRISPR technology.

Environmental Risk Factors There is much more to AD than solely genetics. The environment a person is in greatly affects the probability of developing a disease just as much as his/her genes. This has been seen in twins; one could be diagnosed with AD and only years later will the other develop it as well, if even at all. Epigenetics, the study of how genes can be turned on or off, plays a huge part in a human's ability of developing AD or resisting the disease.

Patients with AD are not the only ones affected. Their family, in particular the ones that act in as their caregivers are often affected the most. It has been calculated that these family members across all patients provide more than 17 billion hours of care for no money in 2012. Those hours are valued at $216 billion.

Genetic Screening - Genetic screening, done by withdrawing blood, can identify which specific risk genes a person may have. But whether you have none or every single allele that puts you at risk, it doesn't determine the certainty of developing Alzheimer's. Too many factors influence its development and progression.

What is Alzheimer's? - Alzheimer's disease or 'AD' was discovered by Alois Alzheimer, a Bavarian psychiatrist with expertise in neuropathology. AD is an irreversible, progressive brain disease. - There is a formation of amyloid plaques (which is an abnormal cluster of protein fragments) and neurofibrillary tangles (which is hyperphosphorylated tau proteins).

Tau protein are proteins that stabilize microtubules which maintain the structure in cells. In the brain, the protein is a main component in the cytoskeleton and are abundant in neurons. They are less common outside of the central nervous system. - Alzheimer's is a loss of concentration between neurons. - There are two types of Alzheimer's: Early-onset Late-onset

o Air pollution o Obesity o Stress, specifically psychosocial stress which is namely depression, anxiety, social isolation, chronic life stress, etc. Exposure to these sort of things is as equivalent as having two APOE4 genes (which is one of the highest risks of influencing the development of AD).

The Mediterranean-Type Diet has actually been studied and shows to be the best diet to avoid developing AD. This diet consists of a high intake of vegetables, legumes, fruits, whole cereals, fish, nuts, unsaturated fatty acids, low to moderate dairy products, low saturated meats, and regular moderate ethanol intake in the form of wine with meals (1 drink a day). Though individuals with the APOE4 allele do not seem to benefit from moderate alcohol consumption.

Late-onset is the Alzheimer's most people develop, which becomes apparent in the mid-60s age range or later. The cause of late-onset is not understood because they compile of many different factors and not every single one applies. It could likely be a combination of genetics, environment, and lifestyle factors that make a person more at risk for developing the disease.

There is no specific gene found yet that causes AD but rather gene risk factors that increase the risk. Late-onset AD risk factors have been found on chromosome 19. Chromosome 19 has the ability to form apolipoprotein E (APOE). - Chromosome 19:

It has been determined that Alzheimer's affects more people than cancer, heart disease, and AIDS combined. It is within the top ten causes of death in the United States and the fifth leading cause for death in people over the age of 65. Only heart disease triumphs the annual care costs of AD.

Yet being such a huge issue, less than 1% of the US government's budget is spent on research for AD. Over the next decade, it is estimated the number of people Alzheimer's affects will increase by 40% and if research dollars still remain unavailable, AD will approximately triple by 2050, leaving 14 million seniors mentally incapable.

With new technology, such as CRISPR that we have been learning about, this creates controversy. While CRISPR has many ethical issues, the ability of being able to edit out APOE alleles and other diseases would be ideal. The APOE allele that actually aids in reducing the risk of AD could be inserted into the genome.

o But being able to impose specific preferences and playing God in unnecessary ways to create a super race is unethical. Many have risen concerns about how children could feel in the future with either having specific traits chosen for them or rather if their parents never underwent genetic screening, and allowed them to inherit unwanted genes.