Spring Research Documentation Sheet Finished

Trey Hughes ISM – Period 7 Lane, C. A., et al. “Alzheimer's Disease.” European Journal of Neurology, John Wiley & Sons, Ltd (10.1111), 19 Oct. 2017, onlinelibrary.wiley.com/doi/full/10.1111/ene.13439. •

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Alzheimer’s has been identified as a public health epidemic and is of major importance. While we do know a lot of the pathology behind Alzheimer’s, as well as what may cause it since its discovery in 1907 by Alois Alzheimer, there has not been a single medication that is able to alter the disease, only able to slightly mitigate its effects. Current studies say that 44 million people across the globe have dementia. This number is expected to triple by 2050 as more and more people age. Around this time, the cost of dementia in the United States is expected to be around $600 billion. In western countries, the risk of Alzheimer’s, particular among men, has dropped recently. It is speculated that this is because of increasing awareness and ability to manage vascular diseases. While it is usually unpredictable, scientists have pinned the mutations of three genes to the pathology of Alzheimer’s: amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). The majority of Alzheimer’s cases involve the complicated relationship between genetics and environmental influences and factors. 70% of Alzheimer’s risk is driven by genetics. The genetics involved in Alzheimer’s can involve many different types of mutations or predispositions, such as the metabolism of cholesterol and microglial activation. Education and exercise are said to protect against Alzheimer’s, while hypertension and diabetes are said to increase risk. The most distinct characteristics of the pathology of Alzheimer’s are amyloid plaques and neurofibrillary tangles. Most of the neurofibrillary tangles are made of the tau protein. This eventually leads to macroscopic atrophy of neurons, causing the brain to shrink in size. The other hypothesis regarding Alzheimer’s pathology is the amyloid hypothesis. This says that when amyloid beta is clipped, and not cleared, tangles form, leading to neurodegeneration. The link between amyloid beta and tau pathology is unclear at the moment. It is believed that the immune system plays a role in Alzheimer’s pathology. The most often presentation of Alzheimer’s is an old individual with increasing problems regarding episodic memory.

This article was very educational about the underlying pathology and statistics regarding dementia and Alzheimer’s, as well as the links between different physiological processes, such as cardiovascular risk and genetic risk .

Trey Hughes ISM – Period 7 Mendiola-Precoma, J, et al. “Therapies for Prevention and Treatment of Alzheimer's Disease.” BioMed Research International, Hindawi Publishing Corporation, 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4980501/. • • • • • • • • • • • • •

Alzheimer’s as a disease is characterized by a blood-brain barrier disruption, oxidative stress, impairment of the mitochondria, inflammation it the brain, and a low metabolic rate. Besides Tau and amyloid beta pathology, decreasing acetylcholine levels and reduced cerebral blood flow has also been observed in Alzheimer’s patients. Pharmaceutical medications can be divided into two distinct groups: symptomatic treatments and etiology-based treatments. Symptomatic medications include acetylcholinesterase inhibitors that stop acetylcholine from being broken down by enzymes, as well as N-methyl-D-aspartate (NMDA) receptor antagonists. This group of medication target the peripheral pathology of Alzheimer’s. Etiology-based medications include secretase inhibitors, amyloid binders, and tau therapies. This group of medication target the main pathology of Alzheimer’s as it is currently understood. 95% of people with Alzheimer’s have sporadic or late-onset AD, which is both influenced and caused by environmental components as well as genetic predisposition to Alzheimer’s. 5% of people with Alzheimer’s have familial or early onset AD, caused by genetic mutations in the APP gene on chromosome 21, the PSEN-1 gene on chromosome 14, and the PSEN-2 gene on chromosome 1. Other forms of treatment of Alzheimer’s include prevention by way of promoting exercise, good mental health, socialization, and a healthy diet. Diagnosis of Alzheimer’s requires a neuropsychological evaluation according to DSM-V criteria among with many other groups. Lab tests, MRI scans, and PET scans are also performed as the disease progresses. Many of the pathological findings come from postmortem brains with AD. Hypercholesterolemia is considered a risk factor for Alzheimer’s. Inhibitors of the phosphorylation of the tau protein such as tideglusib have shown statistically significant benefits. Drugs that treat type II diabetes mellitus have been observed to have a neuroprotective effect in AD.

This article taught me a lot of interesting details about both the peripheral and main pathology of Alzheimer’s, as well as how these two different types of pathology are being treated and tested upon.

Trey Hughes ISM – Period 7 Crous-Bou, Marta, et al. “Alzheimer's Disease Prevention: from Risk Factors to Early Intervention.” Alzheimer's Research & Therapy, BioMed Central, 12 Sept. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5596480/. • • • • • • • • • • • • • • •

Some of the modifiable risk factors for Alzheimer’s disease, as highlighted by the US National Institutes of Health include diabetes mellitus, smoking, depression, mental and physical inactivity and poor diet as risk factors for cognitive decline and AD. A lot of modifiable risk factors related to cardiovascular risk factors, such as diabetes, hypertension, and obesity. It has been proposed that because diabetes disrupts the clearing of amyloid beta clearance, this in turn causes beta amyloid accumulation. Evidence has pointed to the fact that mid-life hypertension can increase the risk of Alzheimer’s by up to 50%. High blood pressure has also been shown to be a risk factor for Alzheimer’s as it could jeopardize the vascular integrity of the blood-brain barrier. Mid-life obesity has been shown to increase Alzheimer’s risk by 60%. Smoking can increase risk of Alzheimer’s because of the oxidative stress and inflammatory responses it causes. Studies have shown that increased physical activity also benefits brain health. The reason for this is that physical activity can activate brain plasticity, vascularization, stimulation of neurogenesis, and reducing inflammation levels In comparison to sedentary behavior, people with high levels of physical activity have been shown to halve their risk for Alzheimer’s. Mediterranean diets have been shown to protect against cognitive decline and can even improve memory and mental health in general. Social and intellectual activity along with high education have also been shown to decrease the risk of dementia and Alzheimer’s. 20% of Alzheimer’s cases worldwide can be attributed to low-education. Bilingualism has been shown to have a beneficial effect on mental health and has even been shown in studies to delay the onset of dementia by 4 years or so. Evidence regarding prevention and avoidance of AD risk factors have been promising on helping fight the disease.

This article was fundamental for me to understand the modifiable and non-modifiable risk factors surrounding Alzheimer’s, and the many treatments that are implemented to treat dementia and Alzheimer’s early.