Risk and Causes of Alzheimer’s Disease
Factors that Contribute to the Risk of Alzheimer’s Disease
Below are some of the factors identified that may contribute to Alzheimer’s disease:
Age is the greatest risk factor for the development of Alzheimer’s disease.
Women have a higher risk of developing Alzheimer’s
Women have a higher risk of developing Alzheimer’s disease, especially those above 85.
Men have been identified to have a less positive survival prognosis (a forecasting of the outcome of a disease) than women.
A person’s risk of developing Alzheimer’s is increased for those with a close relative diagnosed with Alzheimer’s. However, this does not mean that Alzheimer’s is inevitable.
Two categories of genes are responsible for the increase of risk in developing the disease – Risk genes and Deterministic genes.
1. Risk genes:
- These genes increase the likelihood of developing the disease, but this is not a deterministic factor.
- The risk gene with the strongest influence is known as Apolipoprotein E (APOE). This gene encodes a multifunctional protein with significant roles in lipid metabolism and neurobiology.
- Scientists estimated that APOEϵ4 may be a contributing factor in 20 to 25% of all the Alzheimer’s cases.
- Those who have inherited APOEϵ4 from one parent would have an increased risk of developing Alzheimer’s disease.
- Increasing number of APOEϵ4 alleles increases the risk of Alzheimer’s disease from 20% to 90% and decreases the mean age of onset from 84 to 68 years in families afflicted with late-onset Alzheimer’s disease. In these families, homozygosity for APOEϵ4 alleles is basically sufficient to cause Alzheimer’s disease by age of 80 (Corder EH et al., 1993).
2. Deterministic genes:
- These genes directly cause the development of this disease.
- Inheriting the mutation in these genes would guarantee the development of this disease.
- Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD.
There is growing evidences that heart health is connected to brain health. Our brain depends on sufficient supply of oxygen and nutrients supplied through a dense network of blood vessels for normal functioning. Every heartbeat pumps about 20% to 25% of our blood to the head, where brain cells utilise at least 20% of the food and oxygen in the blood. The risk of developing Alzheimer’s disease appears to be increased by many conditions that damage the heart or the blood vessels such as high blood pressure, heart disease, stroke, diabetes and high cholesterol.
Hypercholesterolemia is an initial factor for the development of amyloid plaques by increasing cleavage of amyloid precursor protein (APP) and cholesterol has been shown to be associated with Alzheimer’s disease in later lifetime (Kivipelto et al., 2001). In addition, administration of cholesterol-enriched diet had been shown to increase accumulation of intracellular Aβ in cerebrum of mice (Refolo LM et al., 2001; Shie FS et al., 2002). These data suggested that reducing cholesterol levels in the body might be a practical way to reduce the risk of Alzheimer’s disease.
Head trauma. Serious head injury may increase the risk of developing Alzheimer’s disease. Studies have shown that plaques and tangles are more likely to cause Alzheimer’s symptoms if strokes or damage to the brain’s blood vessels are also present.
Neuronal energy failure. Brain uses energy enormously. However, the brain cells use energy less effectively as we age. Neuronal energy failure is observed in the brain of early stage Alzheimer’s disease.
Poor functioning of blood-brain barrier (a highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system)
Intake of metals particularly aluminum
Various inflammatory processes and cytokines
Causes of Alzheimer’s Disease
Current research is unable to link Alzheimer’s disease to only one cause. Below are some of the causes of Alzheimer’s disease:
APOE (apolipoproteinE) is the most significant genetic risk factor for late-onset cases of Alzheimer’s disease. Scientists estimated that APOEe4 may be a contributing factor of 20% to 25% of all Alzheimer’s disease cases.
- Another causes of Alzheimer’s Disease is decreased synthesis of neurotransmitter acetylcholine due to reduced activity of choline acetyltransferase (ChAT) in the neocortex and hippocampus. Reduction in ChAT is associated with the severity of cognitive impairment in Alzheimer’s patients.
- Attenuated activity of cholinergic neurons (neurons which mainly use acetylcholine to send messages) is a prominent factor of this disease.
- Tau is normally bound to phosphate molecules, as well as microtubules that stabilises its structure.
- In Alzheimer’s disease, large numbers of additional phosphate molecules are bound to tau, causing it to be disassociated from the microtubules to form neurofibrillary tangles within the neuron.
- Microtubules are disintegrated in this process, thereby disrupting the neuron’s internal transport network.
- This disruption destroys communication between the neurons.
Plaques and tangles spread over the cortex during the progression of Alzheimer’s disease.
Plaques (caused by accumulation of amyloid β proteins) and tau protein tangles are the primary abnormal structures that damage and kill neurons.