Alzheimer’s disease results from a combination of genetic, lifestyle and environmental factors that affect the brain over time. A brain affected by Alzheimer’s disease has many fewer cells and many fewer connections among surviving cells than does a healthy brain.As more and more brain cells die, Alzheimer’s leads to significant brain shrinkage. When doctors examine Alzheimer’s brain tissue under the microscope, they see two types of abnormalities that are considered hallmarks of the disease:

  • Plaques: These clumps of a protein called beta-amyloid may damage and destroy brain cells in several ways, including interfering with cell-to-cell communication. Although the ultimate cause of brain-cell death in Alzheimer’s isn’t known, the collection of beta-amyloid on the outside of brain cells is a prime suspect.
  • Tangles: Brain cells depend on an internal support and transport system to carry nutrients and other essential materials throughout their long extensions. This system requires the normal structure and functioning of a protein called tau.
In Alzheimer’s, threads of tau protein twist into abnormal tangles inside brain cells, leading to failure of the transport system. This failure is also strongly implicated in the decline and death of brain cells.

An antibody is a protein produced by the body’s immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly considers healthy tissue a harmful substance. This is called an autoimmune disorder. Each type of antibody is unique and defends the body against one specific type of antigen.

Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. The 20 amino acids that are found within proteins convey a vast array of chemical versatility. The precise amino acid content, and the sequence of those amino acids, of a specific protein, is determined by the sequence of the bases in the gene that encodes that protein. The chemical properties of the amino acids of proteins determine the biological activity of the protein. Proteins not only catalyze all (or most) of the reactions in living cells, they control virtually all-cellular process. In addition, proteins contain within their amino acid sequences the necessary information to determine how that protein will fold into a three dimensional structure, and the stability of the resulting structure.

Plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid comes from a larger protein found in the fatty membrane surrounding nerve cells. Beta-amyloid is chemically “sticky” and gradually builds up into plaques. The most damaging form of beta-amyloid may be groups of a few pieces rather than the plaques themselves. The small clumps may block cell-to-cell signaling at synapses. They may also activate immune system cells that trigger inflammation and devour disabled cells. The build up of beta-amyloid plaques is a hallmark indicator in Alzheimer’s patients.

The blood–brain barrier (BBB) is a highly regulated and efficient barrier that provides a sanctuary to the brain. It is designed to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. Unfortunately, this almost impermeable, highly selective and well-coordinated barrier hampers drug transport to the brain. The BBB is formed by capillary endothelial cells, which are connected by tight junctions with an extremely high electrical resistivity. This barrier allows the passage of water, some gases, and lipid soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function, while blocking out toxic compounds from entering the brain tissue.

The central nervous system (CNS) is the part of the nervous system consisting of the brain and spinal cord. The peripheral nervous system (or PNS) is composed of nerves leading to and from the CNS, often through junctions known as ganglia.

Endothelial cells form the linings of the blood vessels. Endothelial cells have a remarkable capacity to adjust their number and arrangement to suit local requirements. They create an adaptable life-support system, extending by cell migration into almost every region of the body. If it were not for endothelial cells extending and remodeling the network of blood vessels, tissue growth and repair would be impossible.

The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. These cells reduce turbulence of the flow of blood, allowing the fluid to be pumped farther.

Endothelial tissue is a specialized type of epithelium tissue (one of the four types of biological tissue in animals).

The purpose of an enzyme in a cell is to allow the cell to carry out chemical reactions very quickly. These reactions allow the cell to build things or take things apart as needed. This is how a cell grows and reproduces. Enzymes are made from amino acids, and they are proteins. Stringing together between 100 and 1,000 amino acids together in a very specific and unique order forms an enzyme. The chain of amino acids then folds into a unique shape. That shape allows the enzyme to carry out specific chemical reactions — an enzyme acts as a very efficient catalyst for a specific chemical reaction. The enzyme speeds that reaction up tremendously.

A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.

Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective, because of a mutation, the large molecules accumulate within the cell, eventually killing it.

Hunter syndrome develops when a defective chromosome is inherited from the child’s mother. Because of that defective chromosome, an enzyme that’s needed to break down complex sugars called glycosaminoglycans is missing or malfunctioning. The missing or malfunctioning enzyme is called iduronate-2-sulfatase (IDS). In unaffected people, these enzymes are found in parts of the body’s cells known as lysosomes. The lysosomes use enzymes to break down glycosaminoglycans, as part of the body’s normal recycling and renewal process. In a person with Hunter syndrome or another form of MPS, these enzymes either are missing or don’t work correctly. When this enzyme isn’t working properly, undigested glycosaminoglycans collect in the cells, blood and connective tissues, causing permanent and progressive damage. Hunter syndrome and other forms of MPS are sometimes called lysosomal storage diseases.

Hurler syndrome is one of many inherited disorders caused by faulty genes passed on from parents to children. Genes carry a set of instructions that tell the body how to work properly. In Hurler syndrome, the body has a defective gene and cannot make an important enzyme – a deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. Enzymes are proteins inside cells that break down larger building block chemicals into smaller ones. When the body is missing a certain type of enzyme, the cells can’t work properly. In Hurler syndrome, the body is missing an enzyme that breaks down large molecules called glycosaminoglycans (GAG). These molecules help the body build bones and tissue. In patients with Hurler syndrome, the body cannot break down these large molecules. As a result, the GAG molecules build up and damage organs and tissues.

Melanotransferrin is a member of the transferrin family of iron-binding proteins, which also includes serum transferrin, lactoferrin, and ovotransferrin, and it is highly expressed on melanoma cells. Melanotransferrin, also designated p97, shares a high degree of homology with transferrin, but does not play a significant role in the uptake of iron.

Metastatic cancer is cancer that has spread from the place where it first started to another place in the body. A tumor formed by metastatic cancer cells is called a metastatic tumor or a metastasis. The process by which cancer cells spread to other parts of the body is also called metastasis. Metastatic cancer has the same name and the same type of cancer cells as the original, or primary, cancer. For example, breast cancer that spreads to the brain and forms a metastatic tumor is metastatic breast cancer, not brain cancer.

The key elements of an organ essential to its functioning, as distinct from the capsule that encompasses it and other supporting structures.

A peptide is a molecule consisting of 2 or more amino acids. Peptides are smaller than proteins, which are also chains of amino acids. Molecules small enough to be synthesized from the constituent amino acids are, by convention, called peptides rather than proteins. The dividing line is at about 50 amino acids. Depending on the number of amino acids, peptides are called dipeptides, tripeptides, tetrapeptides, and so on.

Pharmacokinetics is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc. Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by enzymes) and the effects and routes of excretion of the metabolites of the drug.

Sandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The most common and severe form of Sandhoff disease becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, children with Sandhoff disease experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some affected children also have enlarged organs (organomegaly) or bone abnormalities. Children with the severe infantile form of Sandhoff disease usually live only into early childhood.

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length. siRNA plays many roles, but it is most notable in the RNA interference (RNAi) pathway, where it interferes with the expression of specific genes with complementary nucleotide sequences. siRNA has the ability to knock down specific disease causing genes to a normal level. siRNA functions by causing mRNA to be broken down after transcription, resulting in no translation. siRNA also acts in RNAi-related pathways, e.g., as an antiviral mechanism or in shaping the chromatin structure of a genome.