Introduction

Scientists have said that the human brain is the most complicated organ in the body—in fact, many claim that it is the single most complex natural or man-made entity on our planet. The mighty brain we carry in our heads processes billions of messages a minute, day and night, week after week, year after year, decade after decade. Its knowledge base expands and grows more complex with every new bit of information acquired, making informed decisions and taking creative leaps based on this new input, all the while retaining the older bits.

Tens of billions of nerve cells, called neurons, most smaller than a grain of sand, are compressed into an incredibly small space about the size of a cantaloupe. Each has a defined function, carrying out billions of distinct communications as we go through our day. At the same time, outside our awareness, the brain regulates breathing, heartbeat, digestion, sensory organs, excretion, and other functions. The brain is so important that even though it accounts for only 2 percent of our body weight, it receives 20 percent of our blood supply.

  • Drawing showing damage caused by AD

  • Doctors track progress by patients clock drawings

  • Two beta-amyloid plaques surrounded by neurons

  • The beta-amyloid cascade begins with cutting of APP

  • Dr. Ron Petersen

  • A method of diagnosing AD is cognitive testing

  • Exercises during cognitive testing

Yet we give little thought to our brain until we encounter a problem in our ability to think. If Alzheimer's disease (AD) develops, the brain slowly loses its ability to make and retrieve memories and process information. A friend's name that was once familiar now eludes us. Last week's Thanksgiving dinner draws a blank. A naval engineer who once performed algebra, calculus, and trigonometry can no longer balance his checkbook. A grandmother cannot recall her family's favorite cookie recipe and is not even safe in the kitchen anymore, as she forgets to shut off the oven. Bits and pieces of life are lost—a doctor's appointment, a child's birth date, the name of a flower, even a spouse's face. Eventually, even simple thinking skills are lost.

We don't yet have all the answers about what triggers the cascade of events that eventually leads to AD, or why some changes in memory and thinking skills that occur even in healthy aging become much more destructive in people who have the disease. But we have learned a lot about the major characteristics of the disease and the way in which it develops over time. We also know that the processes in the brain that lead to the physical and behavioral changes in people with AD begin long before anyone is aware that a problem exists—ten to twenty years before significant memory loss occurs.

Next: The First Discovery

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