Atherosclerosis and Alzheimer's Disease

Dr. Thomas Beach runs the Sun Health Research Institute brain bank in Sun City, Arizona, that Dr. Joe Rogers described earlier. Dr. Beach sees and catalogues many samples of brain tissue that Sun City residents have donated to research after they die. "We have found that Alzheimer's disease patients are about two times more likely to have clogged blood vessels or severe atherosclerosis than people who are cognitively normal." The problem is particularly common in the blood vessels at the base of the brain.

Dr. Beach describes atherosclerosis as inflammation caused by cholesterol deposits on an artery wall. "The deposit is like a little sore, an open wound." The body's white blood cells target the inflammation and try to repair it. The white blood cells and other material released in the healing process slip into the lining of the artery where they accumulate and create more inflammation. Additionally, a fibrous material forms and then hardens within the artery lining. This plaque builds up over time and blocks the flow of blood. "It's shocking the extent to which some of these brain arteries are plugged up by yellowish cholesterol deposits. In some of the arteries, the area for the blood to flow through is extremely small or nonexistent."

"We think that there is definitely some kind of relationship between atherosclerotic vascular disease and Alzheimer's disease. We don't know if it's causative or coincidental. If it is causative, we don't understand the mechanism by which atherosclerosis influences Alzheimer's disease. Inflammation may be behind both." Dr. Beach hypothesizes that certain molecules may start an inflammatory process in brain capillaries. Once this happens, the brain capillaries do not function as well, which may reduce the ability to deliver excess beta-amyloid from the brain to the liver and kidneys for disposal.

"Excess beta-amyloid should cross the capillary wall into the bloodstream. If the capillaries aren't doing their job because of inflammation, they may not be getting rid of beta-amyloid the way they should. The beta-amyloid can accumulate in the brain as amyloid plaques." Dr. Beach agrees with other researchers that the drugs and lifestyle changes that have successfully addressed vascular disease may well prove valuable in the prevention of Alzheimer's disease.

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Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging