A protein present in the human brain, found primarily at the synapses – the junctions between neighboring neurons where the exchange of electrical signals and neuronal communication occurs. Aggregation, or clumping, of alpha-synuclein proteins is a hallmark of Parkinson's disease, a neurodegenerative disorder of the central nervous system. Hsp70, a heat shock protein, has been shown to reduce formation of alpha-synuclein oligomers and reduce associated toxicity.^[1]

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.

A toxic 42 amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer's disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia. Heat shock proteins have been shown to inhibit the early aggregation of amyloid beta 42 and reduce amyloid beta plaque toxicity ^[1].

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.

A lipoprotein produced in the liver and the brain. In the brain, ApoE transports fatty acids and cholesterol to neurons. In the bloodstream, it binds and transports cholesterol, bringing it to tissues and recycling it back to the liver. Approximately 25% of people carry a genetic variant of this lipoprotein called ApoE4, which is associated with higher circulating levels of LDL cholesterol and a 2- to 3-fold increased risk of developing Alzheimer's disease.

Star-shaped cells found in the brain and spinal cord. Astrocytes facilitate neurotransmission, provide nutrients to neurons, maintain neuronal ion balance, and support the blood-brain barrier. Astrocytes also play a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.

The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.

A group of structures in the brain that participate in the initiation and control of movement as well as some cognitive functions. The basal ganglia are embedded deep within the brain's hemispheres and are networked with several other brain structures, including the cerebral cortex, thalamus, and brainstem. Disruption of the basal ganglia network contributes to the pathogenesis of several movement disorders, including Parkinson's disease.

A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.

A highly selective semi-permeable barrier in the brain made up of endothelial cells connected by tight junctions. The blood-brain barrier separates the circulating blood from the brain's extracellular fluid in the central nervous system. Whereas water, lipid-soluble molecules, and some gases can pass through the blood-brain barrier via passive diffusion, molecules such as glucose and amino acids that are crucial to neural function enter via selective transport. The barrier prevents the entry of lipophilic substances that may be neurotoxic via an active transport mechanism.

Clear, colorless liquid present in the brain ventricles and the cranial and spinal subarachnoid spaces. CSF provides protection for the central nervous system and plays a prominent role in brain development and neuronal functioning. CSF is renewed about four times every 24 hours. Low CSF turnover rate, which occurs with aging, leads to accumulation of catabolites in the brain and CSF – such as amyloid beta – that are often observed in certain neurodegenerative conditions such as Alzheimer's 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.

A general term referring to cognitive decline that interferes with normal daily living. Dementia commonly occurs in older age and is characterized by progressive loss of memory, executive function, and reasoning. Approximately 70 percent of all dementia cases are due to Alzheimer’s disease.

An omega-3 fatty acid found in the human brain and the meat of fatty fish. DHA plays a key role in the development of eye and nerve tissues, and is essential for normal brain function in humans. DHA may also reduce the risk of Alzheimer’s disease1 and cardiovascular disease, and may be useful in treating certain inflammatory conditions, such as rheumatoid arthritis. Dietary sources of DHA include krill oil and the meat and roe of salmon, flying fish, and pollock. [1] Patrick, Rhonda P. "Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease." The FASEB Journal (2018): fj-201801412R.

An omega-3 fatty acid found in the meat of fatty fish. EPA reduces inflammation in the body and helps counter oxidative stress in cells. It is crucial for modulating behavior and mood and has demonstrated beneficial effects in managing anxiety and depression. EPA may reduce risk of developing certain chronic diseases such as cancer or cardiovascular disease. Dietary sources of EPA include herring, salmon, eel, shrimp and sturgeon.

A type of cell that forms the endothelium, the thin layer that lines the blood and lymphatic vessels. Endothelial cells regulate blood fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, and platelet aggregation. They are critical players in the body's immune response and resolution of inflammation.^[1]

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.

A protein produced in the liver that plays roles in blood clot formation. Low fibrinogen levels or impaired fibrinogen function can lead to hemorrhage.

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 system that clears the brain of metabolites and other waste. The glymphatic system comprises a vast arrangement of interstitial fluid-filled cavities surrounding the small blood vessels that serve the brain. During sleep, these perivascular structures increase in size by more than 60 percent. This allows a “flushing” operation in which waste products can be eliminated. The glymphatic system also facilitates the distribution of essential nutrients such as glucose, lipids, and amino acids, as well as other substances, such as growth factors and neuromodulators.

A small organ located within the brain's medial temporal lobe. The hippocampus is associated primarily with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation. Amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy in the hippocampus are early indicators of Alzheimer’s disease.

An amino acid present in the blood. Homocysteine is produced during the metabolism of methionine. Abnormalities in methionine metabolism can lead to elevated homocysteine levels, a condition called hyperhomocysteinemia. Elevated homocysteine levels can contribute to arterial plaque formation and increase the risk of clot formation. Some evidence suggests that elevated homocysteine levels double the risk of developing Alzheimer’s disease. Homocysteine levels vary according to dietary intake, with highest levels associated with consumption of animal protein. Variants in the genes that encode for the enzymes that metabolize homocysteine, specifically MTHFR, or methylenetetrahydrofolate reductase, markedly increase the risk of developing a wide array of diseases, including cardiovascular disease, Alzheimer’s disease, and cancer. High intake of dietary folate (present in leafy greens and other fruits and vegetables) can modulate the harmful effects associated with MTHFR.

A region of the forebrain below the thalamus that coordinates both the autonomic nervous system and the activity of the pituitary, controlling body temperature, thirst, hunger, and other homeostatic systems, and involved in sleep and emotional activity.

The chronic, low-grade inflammation that occurs with aging.^[1] Inflammaging is often referred to as "sterile" inflammation because it involves minor immune cell infiltration in the absence of a pathogen.^[2] The processes that drive inflammaging and the pathological conditions that arise because of it are bidirectional and involve multiple physiological processes and pathways.

A member of the specialized pro-resolving mediator family of polyunsaturated fatty acid metabolites. Maresin is produced in macrophages during the metabolism of docosahexaenoic acid (DHA). It exerts anti-inflammatory properties.

An insulating sheath composed of protein and fats that surrounds nerves. Myelin facilitates neural transmission by promoting rapid impulse conduction along axons. It is produced by the Schwann cells in the peripheral nervous system and by the oligodendrocytes in the central nervous system. Demyelinating diseases, such as multiple sclerosis, damage myelin, slowing nerve impulses and eliciting a wide range of neurological complications.^[1]

A rapid-acting transcription factor that responds to harmful cellular stimuli, such as reactive oxygen species, IL-1B, bacterial endotoxin (lipopolysaccharide or "LPS"), ionizing radiation, and oxidized LDL. Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. Several viruses, including the AIDS virus HIV, have binding sites for NF-kB. In the case of HIV, the presence of NF-kB is believed to be involved in switching the virus from a latent to an active state.

A type of glial cell that is involved in the production of myelin, providing support and insulation to axons in the central nervous system. A single oligodendrocyte can extend its processes to 50 axons, wrapping approximately 1 micrometer of myelin sheath around each axon.

A type of polyunsaturated fat that is essential for human health. Omega-3 fatty acids influence cell membrane integrity and affect the function of membrane-bound cellular receptors. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the efficiency of the process varies between individuals.

A laboratory procedure in which the circulatory systems of two distinct organisms are surgically joined, creating a single, shared physiological system. Parabiosis facilitates the study of normal physiology as well as pathological states, such as obesity, diabetes, and the aging process. Studies using heterochronic parabiosis (the joining of organisms of dissimilar ages) have demonstrated that the blood of a young animal has restorative effects on its conjoined, older partner, rejuvenating tissues of the nervous system, skeletal muscle, heart, liver, and other organs.^[1]

A mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms or less. Exposure to air pollution promotes oxidative stress and increases the risk of developing many chronic diseases, including cardiovascular disease, cancer, hypertension, and diabetes. Evidence indicates that global air pollution shortens people’s lives on a scale greater than warfare, other forms of violence, parasitic infection, and more.

The observable physical characteristics of an organism. Phenotype traits include height, weight, metabolic profile, and disease state. An individual’s phenotype is determined by both genetic and environmental factors.

Capable of developing into any type of cell or tissue except those that form a placenta or embryo.

A member of the specialized pro-resolving mediator family of polyunsaturated fatty acid metabolites. Resolvin is produced during the metabolism of omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. It exerts anti-inflammatory effects.

Byproducts of omega-3 fatty acid metabolism. SPMs reduce the inflammation that drives many chronic diseases. Four families of SPMs have been identified and include the resolvins, lipoxins, protectins, and maresins. The SPMs promote apoptosis, regulate leukocyte (white blood cell) activity, and reduce the production of proinflammatory mediators.

Abnormal aggregates of hyperphosphorylated tau, a protein found in the brain. Tau tangles are associated with traumatic brain injury and chronic traumatic encephalopathy and are one of the defining characteristics of Alzheimer’s disease. They inhibit normal brain function, and the degree of cognitive impairment in diseases such as Alzheimer’s is significantly correlated with their presence.

A progressive worsening of memory and other cognitive functions that is thought to be due to chronic reduced blood flow to the brain which is commonly due to the accumulation of cholesterol and other substances in the blood vessel walls that obstruct the flow of blood to the brain.

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]