A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.

Hard, insoluble clumps of amyloid-beta protein. Amyloid plaques are a pathological hallmark of Alzheimer's disease. Formation of amyloid plaques occurs well before symptoms of Alzheimer's disease manifest.

One of three common genetic variants of the APOE (apolipoprotein E) gene. The APOE4 allele, which is present in approximately 10-15% of people, increases the risk of developing Alzheimer's disease and lowers the age of onset. Having one copy of E4 increases risk 2- to 3-fold, while having two copies increases risk as much as 15-fold.

The primary apolipoprotein of chylomicrons, VLDL, IDL, and LDL particles. Apolipoprotein B is produced in the small intestine and the liver. It transports fat molecules (such as cholesterol) to all the body's cells and tissues. High levels of ApoB, especially when LDL particle concentrations are also high, are the primary driver of the formation of plaques that cause vascular disease.

A disease characterized by the deposition of fatty plaques on the inner walls of arteries. Something is said to be atherogenic when it promotes the formation of fatty plaques in the arteries. Atherosclerosis causes coronary artery disease.

Proteins that provide favorable conditions for the correct folding of other proteins. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional form. Group II chaperonins, the variety found in eukaryotic cytosol, are also referred to as CCT, which stands for "chaperonin containing TCP-1."

A subjective rating system used to gauge the perceived intensity of exercise. Borg’s RPE is widely used in biomedical and exercise science research as it provides valuable information for monitoring and prescribing exercise intensity independent of gender, age, exercise modality, and physical activity level.

A large class of diseases that involve the heart or blood vessels, including stroke, hypertension, thrombosis, heart failure, atherosclerosis, and more. Cardiovascular disease is often caused by lifestyle factors. As such, up to 90 percent of cardiovascular disease may be preventable.^[1]

A medical procedure that allows examination of the colon (large intestine). During a colonoscopy, a small camera is inserted into the rectum and colon to search for polyps or cancer or collect bacterial samples for analysis.

A wearable health-monitoring device that measures blood glucose levels in "real-time." Originally designed for people who have diabetes, CGMs demonstrate tremendous value as diagnostic tools, providing a more accurate reflection of glycemic state by directly measuring the postprandial glycemic response to every meal and thereby highlighting individual differences in those responses.

also known as ischemic heart disease (IHD). a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and sudden cardiac death. In 2015 CAD affected 110 million people and resulted in 8.9 million deaths. It makes up 15.9% of all deaths making it the most common cause of death globally.

An imaging test that visualizes blockages in the coronary (heart) arteries. CCTAs are relatively non-invasive, cost-effective measures for low-risk individuals with chest pain.^[1]

A glucocorticoid hormone produced by the adrenal glands. Cortisol levels fluctuate as part of the diurnal cycle and in response to stress and hypoglycemia. Cortisol increases blood sugar, suppresses the immune system, and aids in the metabolism of fat, protein, and carbohydrates.

A ring-shaped protein found in blood plasma. CRP levels rise in response to inflammation and infection or following a heart attack, surgery, or trauma. CRP is one of several proteins often referred to as acute phase reactants. Binding to phosphocholine expressed on the surface of dead or dying cells and some bacteria, CRP activates the complement system and promotes phagocytosis by macrophages, resulting in the clearance of apoptotic cells and bacteria. The high-sensitivity CRP test (hsCRP) measures very precise levels in the blood to identify low levels of inflammation associated with the risk of developing cardiovascular disease.

A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.

The single layer of cells that lines the interior of the blood and lymphatic vessels. The endothelium participates in blood flow, platelet aggregation, and vascular tone. It also regulates inflammation, immune function, and angiogenesis. Endothelial dysfunction is a systemic pathological condition broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium. It is a robust predictor of heart attack and stroke risk.

Endogenous female sex hormones. Estrogens include estrone, estradiol, and estriol. They promote the development and maintenance of secondary sex characteristics in females. Estrogens regulate the menstrual cycle and play key roles in fertility and reproduction. They influence other aspects of health, too, including cognitive function, bone health, and risk of developing cardiovascular disease and cancer.

Flavonoid are widely distributed in plants, fulfilling many functions. Flavonoids have been shown to have a wide range of biological and pharmacological activities in animal, human, and in-vitro studies. Examples include anti-allergic, anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and anti-diarrheal activities.

A hormone produced by the pituitary gland involved in development, growth, pubertal maturation, and reproduction. FSH works together with luteinizing hormone to regulate most reproductive functions.

A series of enzyme-dependent reactions that breaks down glucose. Glycolysis converts glucose into pyruvate, releasing energy and producing ATP and NADH. In humans, glycolysis occurs in the cytosol and does not require oxygen.

Iron overload, also known as hemochromatosis, indicates accumulation of iron in the body from any cause. The most important causes are hereditary haemochromatosis (HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions. Affected individuals over the age of 40 or who have high serum ferritin levels are at risk for developing cirrhosis and have a higher risk of hepatocellular carcinoma as well.

A blood test that measures the amount of glycated hemoglobin in a person’s red blood cells. The hemoglobin A1c test is often used to assess long-term blood glucose control in people with diabetes. Glycation is a chemical process in which a sugar molecule bonds to a lipid or protein molecule, such as hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. Also known as HbA1c.

A circulating lipoprotein that picks up cholesterol in the arteries and deposits it in the liver for reprocessing or excretion. HDL is often referred to as the "good cholesterol."

A condition characterized by abnormally high blood cholesterol concentrations. Hypercholesterolemia is associated with increased risk for cardiovascular disease, particularly coronary artery disease. Treatments for hypercholesterolemia center on dietary and pharmaceutical interventions, such as low-fat diets and statins, respectively.

A physiological condition in which cells fail to respond to the normal functions of the hormone insulin. During insulin resistance, the pancreas produces insulin, but the cells in the body become resistant to its actions and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.

A technique used in analytical chemistry to separate and identify ionized molecules in the gas phase based on their size and shape. IMS is one of four methods commonly used to measure apolipoprotein B,^[1] a marker of cardiovascular disease risk.

A restriction in blood flow to tissues which causes a shortage of oxygen and glucose needed to keep tissue alive. Ischemia usually occurs when blood vessels become clogged and dysfunctional.

Lactate is thought to participate in a sort of "lactate shuttle" where, after being produced in muscle from exercise, it is transported in to tissues like the heart, and brain, where it is used as an energy source. Lactate is one of many molecules that falls under a loose group of molecules referred to as exerkines, a broad group of exercise-induced hormonal-like factors. Evidence suggests that lactate is the preferred fuel of the brain. Additionally, rodent studies suggest that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal brain-derived neurotrophic factor (BDNF) expression.^[1] In clinical studies, lactate shows promise as a treatment for inflammatory conditions including traumatic brain injury and as a means to deliver fuel to working muscles.

A measure of the number of small LDL particles in a person’s blood. LDL-P is thought to be a better predictor of heart attack risk than total LDL cholesterol. Apolipoprotein B (ApoB) is used as a marker for LDL-P since there is one ApoB molecule per LDL particle.

Lipid-protein complexes that allow fats to move through the watery environment inside and outside cells. Lipoproteins emulsify the lipid molecules.

A research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Mendelian randomization studies are less likely to be affected by confounding or reverse causation than other types of studies, but since MR is based on assumptions, the likelihood of the assumptions must be taken into consideration.

A drug commonly used for the treatment of type 2 diabetes. Metformin is in a class of antihyperglycemic drugs called biguanides. It works by decreasing gluconeogenesis in the liver, reducing the amount of sugar absorbed in the gut, and increasing insulin sensitivity. A growing body of evidence indicates that metformin modulates the aging processes to improve healthspan and extend lifespan. Furthermore, metformin may prevent genomic instability by scavenging reactive oxygen species, increasing the activities of antioxidant enzymes, inhibiting macrophage recruitment and inflammatory responses, and stimulating DNA damage responses and DNA repair.[1]

[1] Najafi, Masoud, et al. "Metformin: Prevention of genomic instability and cancer: A review." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 827 (2018): 1-8.

Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.

The process of generating energy that occurs when mitochondria couple oxygen with electrons that have been derived from different food sources including glucose, fatty acids, and amino acids.

A neurodegenerative disorder that affects the central nervous system. Parkinson’s disease is caused by destruction of nerve cells in the part of the brain called the substantia nigra. It typically manifests later in life and is characterized by tremors and a shuffling gait.

An enzyme that participates in cholesterol metabolism by binding to and degrading the receptor for low-density lipoprotein (LDL) cholesterol, thereby influencing blood cholesterol concentrations. People who carry mutations in the PCSK9 gene variant are predisposed to familial hypercholesterolemia (elevated blood cholesterol) due to enhanced PCSK9 activity. PCSK9 inhibitor drugs utilize antibodies that target and bind free plasma PCSK9, promoting its destruction. The PCSK9 gene is a candidate target for gene editing.^[1]

A health condition in which blood glucose levels are higher than normal, but not high enough to indicate a diagnosis of type 2 diabetes. Prediabetes can be halted or reversed with dietary and lifestyle modifications, including weight loss, exercise, and stress reduction.

A female sex hormone produced primarily in the ovaries. Progesterone participates in the menstrual cycle, pregnancy, and embryogenesis. It is the primary pro-gestational hormone in humans and is the dominant hormone in the second half (luteal) phase of the menstrual cycle.

Senescence is a response to stress in which damaged cells suspend normal growth and metabolism. While senescence is vital for embryonic development, wound healing, and cancer immunity, accumulation of senescent cells causes increases inflammation and participates in the phenotype of aging.

A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.

A class of drugs that lower blood cholesterol levels by blocking the production of an enzyme in the liver called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Taking statins may reduce the risk of cardiovascular disease in some people. Although statins are generally well tolerated, as many as 10 – 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems, including issues with forgetfulness, memory loss, and confusion.

The primary male sex hormone. Testosterone is critical to the maintenance of fertility and secondary sexual characteristics in males. Low testosterone levels may increase risk of developing Alzheimer’s disease.

A molecule composed of a glycerol molecule bound to three fatty acids. Triglycerides are the primary component of very-low-density lipoproteins (VLDL). They serve as a source of energy. Triglycerides are metabolized in the intestine, absorbed by intestinal cells, and combined with cholesterol and proteins to form chylomicrons, which are transported in lymph to the bloodstream.

A fat-soluble compound that is present inside the inner-mitochondrial membrane of cells. It plays a role in aerobic cellular respiration which produces energy in the presence of oxygen. The heart, liver, and kidney have the highest CoQ10 concentrations.

A type of lipoprotein. VLDL enables fats and cholesterol to move within the water-based solution of the bloodstream. It is assembled in the liver from triglycerides, cholesterol, and apolipoproteins, and converted in the bloodstream to low-density lipoprotein (LDL). VLDL transports endogenous products (those made by the body), whereas chylomicrons transport exogenous products (those that come from the diet).

An excess of visceral fat, also known as central obesity or abdominal obesity. Visceral fat, in contrast to subcutaneous fat, plays a special role involved in the interrelationship between obesity and systemic inflammation through its secretion of adipokines, which are cytokines (including inflammatory cytokines) that are secreted by adipose tissue. The accumulation of visceral fat is linked to type 2 diabetes, insulin resistance, inflammatory diseases, certain types of cancer, cardiovascular disease, and other obesity-related diseases.^[1]

A specific sequence of DNA located in the promoter region of genes regulated by vitamin D.

The maximum rate of oxygen consumption as measured during incremental exercise and indicates the aerobic fitness of an individual, and plays a role in endurance capacity during prolonged, submaximal exercise.

A training intensity level characterized by sustained, moderate-effort endurance exercise. In zone two, people engage in physical activities that elevate heart rate and breathing, promoting cardiovascular fitness and efficient fat utilization for energy.^[1]