Alzheimer’s DiseaseKennard, J., Patel, K., Pushkarsky, I. & Radhakrishna, R.

Alzheimer's disease (AD) is the most common cause of dementia. It is named after Dr. Alois Alzheimer, who first noticed abnormalities in the brain of a

woman who died due to a mental illness.

Figure 1. Dr Alois Alheimer

Pathophysiology of Alzheimer’s disease The three main features of Alzheimer’s disease are an abnormal level of amyloid plaques and tau tangles and a loss of connection between nerve cells in the brain.

• Plaques are deposits of β amyloid proteins that build up in the spaces between nerve cells

• Tangles are twisted fibres of tau proteins that build up inside cells. The build up of these proteins tend to take place in areas important for memory, such as the hippocampus, which is an area of the brain that is important for the storage of memories, before spreading to other regions.

• Gaps develop in the brain due to the death of brain cells and nerve cells which cannot be regenerated or repaired, resulting in the brain shrinking. There is thinning of the cortical gyri, widening of the sulci, and enlarging of the ventricles. Most of the loss is in the grey. The changes can vary, but losses of more than 40% have been measured in severe cases.

Also, the build up of amyloid and tau proteins become toxic and damage the nerve cells.

 

Figure 2. Cartoon illustation of the changes in neurons Figure 3. Brain cross section with annotations. Healthy vs. and microtubes in Alzheimer’s disease.

There was a recent study involving 17000 patients and 37000 healthy people and it was found that 21 genes enhances the likelihood of developing Alzheimer’s disease. Mutations in any of the 21 genes leads to Alzheimer’s.There are a number of factors thought to increase the risk of developing this condition, including increasing age, a family history of the condition, previous severe head injuries and lifestyle factors and conditions associated with vascular disease.

 

 

  

Figures 4, 5 & 6. cartoon illustrating brain degeneration in Alzheimer’s.

Diagnosis

There is no single test that can show whether a person has Alzheimer's. But there are a few procedures that can be done to distinguish between Alzheimer's disease and other causes of memory loss. The following procedures are:

1. Physical and neurological exam - the doctor will conduct a physical test such as reflexes, muscle tone and strength, sense of sight and hearing, coordination and balance. These tests will check to overall neurological health of the patient.

2. Lab test - A blood test will be taken just to establish if the patients memory loss is due to a thyroid disorder or vitamin deficiencies.

3. Brain imaging – radiological imaging such as structural scanning from CT, MRI or functional imaging from PET scanning will be undertaken, so that any other causes that may affect the brain, such as stroke can accounted for.

Developments

Alzheimer’s disease is the most common form of dementia in the elderly. Statistically there is <0.05% chance of presenting with AD aged under 60. This chance increases to >5% chance for people over 60 and >20% in people over 80. This is matched with a survival period of ~ 6 years in developed countries.

Due to the overall global aging population, the amount of people being diagnosed with Alzheimer’s disease is increasing yearly. This means there is a greater and greater push to fully understand the disease and cure it.

There are many research projects that are currently taking place. i.e. for the cause and cure of Alzheimer’s disease. Cause – Currently the University of Oxford are investigating the interactions that

cause tau to form tangles in Alzheimer's disease Cure – The University of St Andrews is currently researching on Novel drugs for

treating Alzheimer's disease.

Treatment

There is currently no cure for Alzheimer’s disease, but there are some drugs that relieve or slow down some of the symptoms. Drugs such as Aricept, Exelon and Reminyl are commonly used for patients with Alzheimer’s disease as they maintain the supply of acetylcholine in the brain.

The initial symptoms of dementia prior to AD diagnosis include: Amnesia – Loss of memoryAphasia – Difficulty speaking, using incorrect sounds or words.Apraxia – the inability to carry out tasks even though the sensory and motor systems are intact.Agnosia – Inability to recognise things/people including your own reflection.

Referenceshttp://www.alz.co.uk/info/alzheimers-diseasehttp://www.alz.org/braintour/healthy_vs_alzheimers.asphttp://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.htmlhttp://www.alz.org/alzheimers_disease_what_is_alzheimers.asphttp://www.nhs.uk/Conditions/Alzheimers-disease/Pages/Introduction.aspxhttp://www.alz.org/braintour/plaques.aspDawbarn, D. & Allen, S, J,. (2001). Neurobiology of alzheimer’s disease. (2nd ed.). Oxford: Oxford University Press.http://emedicine.medscape.com/article/1134817-clinical#a0256http://www.alzheimers.org.uk/

Healthy Brain:The cerebrum is involved in; problem solving, thinking, feeling, remembering. The cortex (outer layer of the cerebrum) is involved in interpreting signals from the outside world like sounds, smells and sights. It generates thoughts and makes plans as well as forming and storing memories and controlling  movement.

Mild AD:Brain volume has decreased. This is due to neuronal cell death throughout the brain caused by AD. This effects overall performance of the brain. The shrinking cortex has started causing problems with thinking, planning and remembering. The Hippocampus is affected to a greater degree than other areas, making it harder to store new memories. The cerebrospinal fluid ventricles start filling to a greater degree, increasing in size. 

Severe AD:Plaques are formed from protein fragments and tangled dead nerve cells. These plaques prevent neurotransmitter movement in the synapses, therefore preventing signals from being passed on through the synapse.This starts a snowballing effect on the whole system. The lack of signals cause the immune system to attack the nerve cells and cause inflammation in the area. The inflammation physically disrupts the channels and vessels that carry oxygen and nutrients. This causes further cell death and formation of plaques. This explains why AD may start 20 years before diagnosis but is progression becomes faster and it doesn't stop. 

The production of certain chemicals in the brain, such as acetylcholine is affected. Acetylcholine has various functions in the central nervous system, including playing a large role in learning and memory formation. . Consequently, the gaps that develop in the brain are mainly in the temporal lobe and hippocampus. This in turn leads to memory loss and other symptoms of Alzheimer’s.

Figure 7. comparative positron emissiontomography of healthy vs. Alzheimer’s disease.

Figure 8. graph illustrating increase in prevalence and Alzheimer’s disease in different age groups.

Figure 9. Graph demonstating changes in survival rates in different pathological conditions.

Figure 10. image showing various related symptoms in Alzhiemer’s. Figure 11. visual representation of some of the effects of Alzheimer’s.