Plaques and Tangles: The Hallmarks of AD
Alzheimer's disease disrupts each of the three processes that keep neurons healthy: communication, metabolism, and repair. This disruption causes certain nerve cells in the brain to stop working, lose connections with other nerve cells, and finally, die. The destruction and death of nerve cells causes the memory failure, personality changes, problems in carrying out daily activities, and other features of the disease.

The brains of AD patients have an abundance of two abnormal structures - beta amyloid plaques and neurofibrillary tangles. This is especially true in certain regions of the brain that are important in memory. Plaques are dense, mostly insoluble (cannot be dissolved) deposits of protein and cellular material outside and around the neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent. Scientists have known about plaques and tangles for many years, but recent research has shown much about what they are made of, how they form, and their possible roles in AD.

Amyloid Plaques
Plaques are made of beta-amyloid, a protein fragment snipped from a larger protein called amyloid precursor protein (APP). These fragments clump together and are mixed with other molecules, neurons, and non-nerve cells. In AD, plaques develop in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are used in thinking and making decisions. We still don't know whether beta-amyloid plaques themselves cause AD or whether they are a by-product of the AD process. We do know that changes in APP structure can cause a rare, inherited form of AD.

From APP to Beta-amyloid
APP is a protein that appears to be important in helping neurons grow and survive. APP may help damaged neurons repair themselves and may help parts of neurons grow after brain injury. In AD, something causes APP to be snipped into fragments, one of which is called beta-amyloid; the beta-amyloid fragments eventually clump together into plaques.

APP is associated with the cell membrane, the thin barrier that encloses the cell. After it is made, APP sticks through the neuron's membrane, partly inside and partly outside the cell.

Enzymes (substances that cause or speed up a chemical reaction) act on the APP and cut it into fragments of protein, one of which is called beta-amyloid.

The beta-amyloid fragments begin coming together into clumps outside the cell, then join other molecules and non-nerve cells to form insoluble plaques.

Neurofibrillary Tangles
Healthy neurons have an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A special kind of protein, tau, makes the microtubules stable. In AD, tau is changed chemically. It begins to pair with other threads of tau and they become tangled up together. When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.