Alzheimer's disease

Alzheimer’s disease is a type of Dementia, accounting for 62% of Dementia cases in the UK. It is a neurodegenerative disorder (affecting the brain and becoming progressively worse with time) found predominantly in elderly people, with the incidence of the disease doubling with every 5 year increase in age above 65 years.  There is also a rare form of the disease known as early onset familial Alzheimer’s disease which is inherited and occurs in people aged between 30 and 60. The disease will present slightly differently in each person with the illness, but is characterised by a decline in brain function, such as memory loss, impaired speech and vision, disorientation, delusions and changes to behaviour and personality.

The brain is made of nerve cells known as neurons, these cells carry electrical impulses and between the neurons there are gaps known as synapses, across which chemicals known as neurotransmitters diffuse, to pass the impulse from one neuron to another, enabling us to respond to both internal and external stimuli. In Alzheimer’s disease, several changes occur within the brain, including the destruction of the neuron and synapses resulting in the atrophy (severe reduction in size due to wasting away) of certain regions of the brain. In the cells of a healthy brain, a fibrous protein known as tau is produced, and is essential for maintaining the size and shape of nerve cells and ensuring effective cell communication. In those with Alzheimer’s an abnormal version of tau is produced, which cannot carry out these functions and accumulates in, what are known as, neurofibrillary tangles, disrupting the communication between cells and causing the disintegration of the microtubules that maintain cell structure, eventually leading to cell death. Additionally, in the brains of people who have Alzheimer’s disease, neuritic plaques form. This is the accumulation of a small protein known as beta amyloid, which is produced when APP (amyloid precursor protein) is broken down. Beta amyloid is broken down healthy people, but not in Alzheimer’s disease, therefore it forms plaques around the nerve cells which are thought to be toxic to the cells, causing changes leading to cell death. The changes in Alzheimer’s first occur in the hippocampus region of the brain which is responsible for forming and storing memories. The changes then spread to the cerebral cortex and the frontal (skilled movements and problem solving), temporal (language and hearing) and parietal (sensory abilities such as pain response) lobes. The region known as the basal nucleus of Meynert undergoes degeneration in Alzheimer’s disease. This region is normally rich in neurons using the neurotransmitter acetylcholine, which is thought to be important in memory, however, this degeneration means that the brain produces less acetylcholine.

Alzheimer’s disease is categorised as either mild (usually involving: forgetfulness; mood swings; speech impairment and withdrawing from social situations), moderate (often with symptoms such as: disorientation and problems with spatial reasoning; problems with eyesight; hallucinations; obsessive behaviour; insomnia; incontinence and frustration or depression resulting from confusion and inability to carry out tasks) or severe (likely to display many of the symptoms listed above in addition to: a complete loss of short and long-term memory; hallucinations causing the person with Alzheimer’s to become distressed, violent and suspicious of those around them; self-neglect; difficulty moving or swallowing and a loss of appetite, due to forgetting when they have begun these tasks). The symptoms of Alzheimer’s may also be seen in individuals who are suffering from strokes, brain tumors, multiple sclerosis, thyroid dysfunction, infectious diseases such as HIV and syphilis, substance abuse or the side effects of some medications; it is important to first eliminate any of these, more-treatable conditions as the cause of the symptoms. As a result, Alzheimer’s diagnosis can take some time. The diagnosis of Alzheimer’s will usually involve neurological examination, potentially followed by CT (using x-rays) or MRI (using a magnetic field and radio waves) scans of the brain. Severe Alzheimer’s can lead to compromised immunity and life threatening infections, so as the disease develops, full-time care is needed to support the person with Alzheimer’s disease. Most people with Alzheimer’s disease die with the illness rather than from it, however, there is a significantly reduced the quality of life for those with the disease.

There is no cure for Alzheimer’s disease, however there are a few drugs which have been shown to alleviate some of the symptoms of the disease. Donepezil, galantimine, rivastigmine and memantine are drugs that are currently prescribed for Alzheimer’s treatment. The first three drugs are acetylcholinesterase inhibitors and prevent the breakdown of the neurotransmitter acetylcholine, in an attempt to maintain the levels of this chemical and communication between nerve cells, however they can have the side effects of nausea, diarrhoea and fatigue. Memantine blocks the chemical glutamate which is released in excessive amounts in Alzheimer’s disease and can damage the brain cells. It is also important to treat the psychiatric problems that may present alongside the disease, and incorporate memory aiding activities into day-to-day life such as labelling cupboards, making timetables and diaries and keeping useful addresses and telephone numbers to hand.

The reasons for the brain deterioration in Alzheimer’s are not entirely known, however there are several factors which may increase the risk of developing the disease. Incidence of Alzheimer’s disease is significantly correlated with increasing age, however, it is also thought that lifestyle factors such as keeping mentally and physically active can reduce the risk of Alzheimer’s whereas high blood pressure, high blood cholesterol and smoking increase the risk. Severe head trauma, whiplash injuries and repetitive head injuries such as from boxing can lead to an increased risk of developing Alzheimer’s in later life. People with Down Syndrome who live over the age of 50 are at an increased risk of developing Alzheimer’s, they have an extra copy of Chromosome 21, so have extra copies of the gene producing the protein RCAN1 therefore the protein is produced in excess and can cause neuronal death. The overexpression of this gene can also be caused by stroke, high blood pressure and high levels of beta amyloid.

The influence of inheritance on developing late-onset Alzheimer’s is not very significant, however, recently several genes have been identified as playing a role in the biochemical changes that occur in Alzheimer’s. One particular gene involved in Alzheimer’s is the gene apoE that codes for the protein apolipoprotein E, which carries fat molecules in the brain and are thought to be involved in the breakdown of beta amyloid. This gene has three different alleles (different versions of the same gene), apoE2, apoE3 and apoE4.  The proteins coded for by the genes apoE2 and apoE3 are large protein molecules that effectively transport fats and so can breakdown the plaques, but by apoE4, the protein is a small molecule which is easily degraded so cannot carry out these functions. In some populations, though not all, if a person has one or more copy of the apoE4 allele, they have a greater chance of developing late onset Alzheimer’s, those who are heterozygous (have 1 copy of the apoE4 allele and 1 copy of another allele) have a three times greater risk and homozygotes (who have 2 copies of the apoE4) have a ten times greater risk of developing the condition.

Recent research has identified 11 new genes linked to Alzheimer’s. The study comparing the genetic information of Alzheimer’s patients and healthy volunteers (as controls) has shown that at least 20 genes are involved in late-onset Alzheimer’s, as are significantly more common in those with the disease. The findings are useful as they can provide further information on the biological pathways involved in the disease, and although at the moment there are no preventative drugs against Alzheimer’s disease, if they were developed, this information could be used to screen and identify those at risk in the population. The findings suggest that changes in the inflammatory response, immune system and neuronal communication all affect the progression of the disease.                

Additionally, there has been research into a pill to combat degenerative brain diseases and neuronal death due to the accumulation of protein. This particular study looked at prion (a protein) diseases such as CJD however the biological causes of these diseases are similar to those involved in Alzheimer’s. The study showed that over the 5 week study, mice remained free of symptoms such as memory loss and impaired reflexes, as well as living longer than untreated animals. Although the same effects may not be true for Alzheimer’s in humans and drugs suitable for human trials are unlikely to be developed for many years, this study offers hope into the development of a cure for Alzheimer’s disease in the future.

http://www.nhs.uk/Conditions/Alzheimers-disease/Pages/Introduction.aspx

http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=100

http://www.theguardian.com/science/2013/oct/27/alzheimers-study-new-genes-implicated

http://www.theguardian.com/science/2013/oct/10/study-gives-hope-alzheimers-pill