The exact cause of Alzheimer’s is not known to researchers till date. In most of cases, death of brain cells occur as it is a progressive neurodegenerative disease. The cause of early onset of Alzheimer’s is related to genetic mutation and of late onset to the successive brain changes over the period of time. But scientists and researchers relate the causes to the most studied and tested hypothesis ‘amyloid cascade hypothesis.’ Therefore, it is assumed that the cause of the disease is related to a combination of genetic, environmental and lifestyle factors. Environmental and lifestyle factors are generally considered as risk factors for a person to get the disease and not as precise causes as such. Scientists observed plaque formation, nerve tangling and genetic mutation and inheritability as major causes that may cause Alzheimer’s.
Usually old people get AD but it is not related to age at all and is not considered as a result of the process of ageing. It occurs due to loss of brain cells and deterioration that may lead to damage of neurotransmitters (which help in communication of nerve cells in the brain). Damage of the brain cells and plaque formations with tangled fibres are usually seen in people upon brain examination.
Two main forms of nerve damage is related to gradual loss of the brain function in such people who have Alzheimer’s –
• Protein deposits known as plaques build up in the brain
• Nerve cells develop tangles (neurofibrillary tangles)
Plaques build up in brain:
Amyloid Cascade Hypothesis is based on plaques build up and its deposition in the brain. The deposition of beta-amyloid protein around brain cells occurs which results in the formation of plaques which block brain cells signalling and gradually damage and cause the death of brain cells. Scientists do not know the exact reason of formation of these plaques but one of the theories tells that normally occurring blood protein which is required for the transport of fatty substances in the body called ApoE (apolipoprotein E) is responsible for plaques formation in the brain. The form of ApoE is genetically determined in each person. There are various types of ApoE proteins present in our body and some of them are considered to be associated with higher risks of Alzheimer’s. It may be possible that certain types of ApoE damages the nerve cells. It is seen that people with high blood pressure and high cholesterol level are at greater risk of getting Alzheimer’s. It may be possible that ApoE in combination with other substances lead to plaque formation.
Nerve cell Tangles (Neurofibrillary or tau tangles):
Neuro-fibrillary tangles are made up of protein called tau protein which helps brain cell to communicate. Brain cells depend on tau proteins for internal support and transport nutrients and other essential materials inside the brain. The threads of tau proteins get twisted and tangled with each other forming nerve tangles which lead to death of some nerve cells making communication impossible and also damage to transport system that lead to death of brain cells eventually due to lack of nutrients.
When brain cells die, it causes the brain to shrink which then causes improper brain function and damage to the brain eventually. All these factors cause problems in intelligence, memory, language, and behaviour of a person. The plaques and tangles are not seen in people who do not have Alzheimer’s.
Mostly, Alzheimer’s disease occurs in old age after 60 years. Genetics and gene hereditary is considered as one of the main causes of the disease. Most of the people who have a family history of Alzheimer’s and whose siblings suffer from it are likely to get affected and develop the disease.
There are two types of genes which determine whether a person may develop Alzheimer’s:
Risk genes: This gene increases the risk of developing the Alzheimer’s but it does not necessarily cause the disease. Researchers found that the late onset of Alzheimer’s is related to apoprotein E gene. This gene has various forms. Mutations in any of these genes may lead to early onset of the disease. Types of APOE genes are APOE-e2, e4-3 and e-4. Early onset of Alzheimer’s is related to gene APOE e-4. A person who carries a single copy of it is at a risk of getting the disease and if the person carries two copies, he is at a higher risk of getting the disease. Early onset of Alzheimer’s occurs between the age of 30s and mid 60s in a person and accounts for less than 10% of all people suffering from it. People carrying APOE e-4 gene doesn’t mean they will always get Alzheimer’s. Even people who do not have this gene may also get this disease.
Deterministic genes: These genes always cause Alzheimer’s if inherited by a person. Variations in gene coding of any of these three proteins – amyloid precursor protein (APP), presenilin – 1 and 2 (PS-1 and PS-2) lead to the development of Alzheimer’s directly. Autosomal Dominant Alzheimer’s Disease (ADAD) or Familial Alzheimer’s Disease is a type of Alzheimer’s which is defined as dominantly inherited Alzheimer’s disease with pathological confirmations. People who carry these genes generally develop AD in their 40s or 50s. These gene variations are found in only few hundred families worldwide. Familial Alzheimer’s truly accounts for only 1% of cases around the world.
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