The Effects of Alzheimer's on the Brain

Alzheimer's disease is a degenerative disease of the brain. Understanding how the anatomy of the Alzheimer's brain differs from a normal brain gives us insight. It can help us cope better with the changes that happen to our loved ones as a result of this debilitating disease.

In Alzheimer's disease, the appearance of the Alzheimer's affected brain is very different to a normal brain. The cerebral cortex atrophies. That means that this area of the brain shrinks and this shrinkage is dramatically different from the cerebral cortex of a normal brain. The cerebral cortex is the outer surface of the brain. It is responsible for all intellectual functioning. There are two major changes that can be observed in the brain using magnetic resonance imaging (MRI):

• The amount of brain substance in the folds of the brain (the gyri) is decreased
• The spaces in the folds of the brain (the sulci) are grossly enlarged.

Microscopically there are a number of changes in the brain too. These can only be viewed histologically with tissue samples taken at autopsy.

At the microscopic level, the two hallmark findings in the Alzheimer's brain are amyloid plaques and neurofibrillary tangles. Amyloid plaques are found outside the neurons, neurofibrillary tangles are found inside the neurons. Neurons are the nerve cells within the brain.

These plaques and tangles are also found in the brains of people without Alzheimer's. It is the density and location of them that is significant in Alzheimer's disease. These plaques and tangles cause death and shrinkage of neurons, and cause the brain to atrophy.

The Role of Amyloid Plaques

Amyloid plaques are mostly made up of a protein called B-amyloid protein which is itself part of a much larger protein called APP (amyloid precursor protein). These are amino acids.

We do not know what APP does. But we do know that APP is made in the cell, transported to the cell membrane and later broken down. Two major pathways are involved in breakdown of APP (amyloid precursor protein). One pathway is normal and causes no problem. The second results in the changes seen in Alzheimer's and in some of the other dementias.

Pathway Breakdown Leading to Alzheimer's Damage

In the second breakdown pathway APP is split by enzymes β -secretase (β=beta) then γ-secretase (γ=gamma). Some of the fragments (called peptides) that result stick together and form a short chain called an oligomer. Oligomers are also known as ADDL, amyloid-beta derived diffusible ligands. Oligomers of amyloid beta 42 type (Aβ42) have been shown to be highly toxic. Aβ42 produces tiny fibers, or fibrils, and when they stick together they form an amyloid plaque that collects between neurons, causing dysfunction of cell to cell communication at the synapse.

The Role of Neurofibrillary Tangles

The second major finding in the Alzheimer's brain is neurofibrillary tangles. These tangles are composed of Tau proteins, which play a crucial role in the normal structure and function of the neuron. In people with Alzheimer's disease, the formally straight Tau proteins have mutated, due to overactive enzymes, resulting in twisted strands that aggregate together and become tangles. These tangles acculumulate inside the neuron, disrupt cell activity (movement of nutrients and essential supplies), and result in the death of the neuron.

Alzheimer's Brain Summary

The role of amyloid plaques and neurofibrillary tangles on the functioning of the brain is by no means fully understood. Most people with Alzheimer's disease show evidence of both plaques and tangles, but a small number of people with Alzheimer's only have plaques and some have only neurofibrillary tangles.

People with plaque only Alzheimer's show a slower rate of deterioration during their lives. Neurofibrillary tangles are also a feature of a different degenerative brain disease called frontotemporal dementia.

Research into Alzheimer's disease is finding out more and more about the anatomy and physiology of the brain. As we understand more about the role of plaques and tangles observed in the Alzheimer's brain the closer we get to a significant breakthrough and a cure for Alzheimer's disease.