What exactly is Alzheimer’s Disease?

 

The History

 

Alzheimer’s disease is the most common cause of dementia which is irreversible and induces progressive deterioration of neurones in the brain. Named after Alois Alzheimer a German Physiatrist who first described its symptoms in 1901, after realising his patient, 51-year-old female, Auguste Deter’s progressive mental deterioration. Her autopsy revealed an atrophied cerebral cortex, widening of sulci and what we now know as neurofibrillary tangles and neurotic plaques. (Shampo et al. 2013) which confirmed Alzheimer’s suspicions of irregularities in the brains structure.

Dementia is a syndrome resulting from a group of related symptoms including; short term memory loss, drastic mood changes, disorientation, anxiety, difficulties with thinking and problem solving. These symptoms can cause personality changes and lead to increased aggression. More than 850,000 people in the UK are affected by Alzheimer’s disease (NHS, 2020).

The image below shows the difference in brain structure of a healthy brain compared with the brain of an individual with advanced Alzheimer’s. Individuals with advanced Alzheimer’s show a significant decrease in brain mass. Older individuals display severe changes to grey matter with age being the most important risk factor for Alzheimer disease (Neurology, 2009) It is thought by scientists that changes in the brains begin a decade or more before symptoms begin to show or cognitive problems start to develop. ‘During this preclinical stage of Alzheimer’s disease, people seem to be symptom-free, but toxic changes are taking place in the brain’. (NIH, 2019) Atrophy (deterioration of the brain tissue) starts in the hippocampus then progresses to the cortex (outermost layer) of the brain. Both essential for forming new memories and involved with learning and emotions. ‘As more neurons die, additional parts of the brain are affected and begin to shrink. By the final stage of Alzheimer’s, damage is widespread, and brain tissue has shrunk significantly’. (NIH, 2019)

 

 

Development of Alzheimer’s disease

Sticky β-amyloid proteins which have the tendency to clump together form plaques (abnormal clusters of protein) which block communication and signalling between cells. These clumped plaques can also trigger immune reactions that cause destruction of nerve cells. Usually, the tau protein stabilises microtubules, which form the cytoskeleton within eukaryotic cells, in the brain. Microtubules maintain the integrity of the cell and enables efficient cell communication. With Individuals with Alzheimer’s the tau protein collapses into twisted strands known as (neurofibrillary) tangles disintegrating the microtubules and preventing nutrients from reaching neurones, ultimately leading to cell death.

Effects of plaques and tangles

The accumulation of plaques and tangles begin in the hippocampus, responsible for forming memories and learning. Theses plaques and tangles then invade other parts of the brain inducing changes to the brain’s structure. In the frontal lobe these proteins destroy the ability to process complex thoughts and problem solve. Erratic mood swings are a result of these proteins in the limbic system. Once the proteins migrate to the occipital lobe (towards the back of the brain) long term memory deteriorates rapidly. (Alzheimer’s association, 2020) In later stages, the medulla oblangata, responsible for regulating heart rate and respiration via the autonomic nervous system stops working effectively which could result in death or severe permanent brain damage.

Treatment and Research

 Researchers have been working tirelessly to understand more about the progression of the disease and in recent years have focussed on slowing down its progression. Acetylcholine (Ach), an important neurotransmitter is decreased in Individuals with Alzheimer’s. Acetylcholine therapy uses drugs such as Rivastigmine to reduce the breakdown of Ach however this is only temporary. More information is needed to fully decipher the mechanism in which Alzheimer’s disease progresses before a cure can be found.

Scientists continue to work on decoding the puzzle that is Alzheimer’s disease and here at Lancaster University Scientists are working on stopping the tau protein from forming plaques and tangles. In the labs here at Lancaster, researchers have identified an inhibitor which could prevent the formation of these. Before testing on humans can begin, testing on models will first go ahead. Dr Norah Ulzheimer currently works on brain cells grown in a dish and treated with chemicals until they resemble brain cells in Alzheimer’s patients. The tau proteins are also created in the lab and injected directly into the model cells. Half of the cells will be treated with the inhibitor and the other half will act as the control so comparisons can be made, and changes can be monitored.

A lot of hard work is being put into Alzheimer’s research as the need for more effective treatment is required to decrease the larger numbers affected by Alzheimer’s we have seen in the last few years. Below are some Charities and research groups studying Alzheimer’s who can provide more information and where donations can be made.

Alzheimer’s association, https://www.alz.org/

Alzheimer’s Research UK, https://www.alzheimersresearchuk.org/

Alzheimer’s Society, https://www.alzheimers.org.uk/

Defying Dementia, https://www.lancaster.ac.uk/giving/defying-dementia/

Dementia UK, www.dementiauk.org

NHS, https://www.england.nhs.uk/mental-health/dementia/research/

 

References

NHS, 2020, About dementia [Online] Available at: https://www.nhs.uk/conditions/dementia/about/ [Accessed 24-09-20]

NIH, 2019, Alzheimer’s Disease Fact Sheet, available at: https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet [Accessed 05-10-20]

Raji, C. A., Lopez, O. L., Kuller, L. H., Carmichael, O. T., Becker, J. T., 2009, Neurology, Age, Alzheimer disease, and brain structure

Shampo, A. M., Kyle, A. R., Steensma, P. D., 2013, Stam vignette on medical science, Mayo Clinic Proceedings

Alzheimer’s association, 2020, Inside the Brain, A tour of how the mind works, available at: https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2 [Accessed 06-10-20]