What is Alzheimer’s Disease?

An amyloid plaque, here labelled in blue, is surrounded by misshapen neurons (green) to the top right and bottom left, and a swollen axon to the bottom right.Alzheimer’s Disease is a progressive degenerative disorder of the brain resulting severe loss of memory (dementia).  All of us experience memory lapses from time to time, but in Alzheimer’s disease this loss goes beyond forgetting where you left your car key.

Childhood memories, the faces of loved ones, and even basic bodily functions can be lost in the disease course. It mainly affects individuals over 65 years of age, with rare cases seen in younger individuals (early-onset Alzheimer’s).

The image shows an amyloid plaque (blue) surrounded by misshapen neurons (green) to the top right and bottom left, and a swollen axon to the bottom right. 

What causes it?

Major risk factors for Alzheimer’s disease include ageing, genetics, poor diet, lack of exercise and head injury. Within the brain there is extensive and progressive loss of neurons and synapses (the chemical junctions allowing communication between neurons).

Neurons are the electrically excitable cells in the brain that transmit information and form networks. Unlike other cells, such as those that make up our skin, neurons do not continue multiplying after we are born, so any loss is permanent. But what causes the neurons to die? Some clues come from looking at the brains of patients who died from Alzheimer’s and the genetics of the (rare) inherited cases of the disorder.

Post-mortem brain samples reveal two types pathological protein deposits; plaques (composed of amyloid) and tangles (composed of a different protein called tau). Plaques lie outside of cells and you often see dystrophic (unhealthy and swollen) neurons surrounding these deposits. 

Tangles, on the other hand, are found inside neurons, and seem to disrupt the movement of cellular proteins (axonal transport) within the cells. Although it has been shown that memory loss is worse in patients with greater numbers of tangles; mutations in the amyloid protein, and the enzymes that process it, are found in families who have a strong tendency to develop the disorder.

Patient’s with Down syndrome, who naturally overproduce amyloid protein, are also much more likely to develop the disease.

What are scientists trying to do about it?

Current clinical research is focusing on how to target the early stages of the disease, before permanent loss of neurons. This is being done by searching for biomarkers (molecules that change along with the disease course) in blood or other biological samples. Brain scans using PET or MRI can now detect amyloid, tau and brain shrinkage even before symptoms begin.

Population wide genetic studies are also being carried out to work out what makes someone more, or less, likely to develop Alzheimer’s. By targeting appropriate patients and catching the disease early the ultimate aim is to stop the disease in its tracks or perhaps even repair some of the damage already done.

Understanding what happens to the brain in the early stages of the disease is a vital part of Alzheimer’s research, because this is when drugs are most likely to be effective. Many groups work on the cellular and molecular alterations in the disease, and study the close interactions between different cell types in the brain.

Some aspects of the disease can be modelled in animals such as transgenic mice, or in cell cultures, and this work is vital for understanding these early stages. By mapping out a detailed timeline of what happens in the brain as the disease progresses, scientists hope to find targets for drug development. 

Ongoing research in the Coleman Lab

Our lab works with models of Alzheimer’s disease to study what happens to the brain and nerves over the disease course. We particularly focus on axonal transport; the movement of vital cell components along neurons, as a potential issue in the disease. Axons show large swellings around plaques [brain.oxfordjournals.org/content/132/2/402.long] and there is disruption of microtubules “the railway tracks of nerves that allow transport to happen” at these points.

If, over time, transport became less and less effective, neurons could be starved of vital nutrients, leading the extensive loss of these cells in the disease. We are currently modelling disease progression by culturing brain slices in a dish, the aim here to determine whether changes in transport can be detected and if so, prevented. The slice model also allows us to test which compounds can alter disease progression and closely study changes on a cellular and molecular level.

Members of our group also coordinate the Alzheimer’s Research UK Cambridge Network which promotes interactions between local scientists working on dementia and organises public engagement activities. 

For further information on Alzheimer’s disease research see: