Alzheimer is a common disease, related to aging. A progressive disease that destroys memory and other important mental functions. It’s scary to think of Alzheimer’s disease (AD) as the 6th leading cause of death in the United States.
How can we prevent developing AD, when we get older?
Cause of Alzheimer’s disease
Many studies showed that the inappropriately turning on/off of PI3K/ Akt/ mTOR signaling pathway is a causative node in Alzheimer’s disease (AD).
Products from constant activation of PI3K/ Akt/ mTOR signaling pathway
Generally, after the pathway is activated, it phosphorylates Akt in downstream, leading to variety of phosphorylation in different substrates. For example, both FOXO and GSK3β are inactivated, result in reducing stress resistance, DNA repair and induction of glycogen synthesis and lipid synthesis, respectively. Akt also activates mTOR, increasing inactive IRS-1 and decreasing IRS -1/2. Later on, the insulin receptor substrate (IRS) is dysfunction, developing insulin and IGF-1 resistance.
In addition, PI3K/ Akt/ mTOR signaling pathway also produces tau and Aβ. The hyperphosphorylated tau protein leads to neurofibrillary tangles (NFT), known as a primary marker of Alzheimer’s disease. It is linked to cognitive decline and synaptic loss, particularly in glutamatergic neurotransmission. In addition, the overload Aβ oligomers leads to inappropriately increased activation of PI3K/ Akt / mTOR signaling pathway through increasing levels of IRS-1 phosphorylation and thereby contribute to insulin resistance.
There are many risk factors distributing to Alzheimer’s disease, besides aging and diabetes:
- Genetic factor: those, who have family history with Alzheimer’s disease (AD), they will have a higher chance to develop it at young age. The risk genes are apolipoprotein E-e4 or APOE-e4/ -e2/ -e3. There is a genetic test available for APOE-e4 and the other rare genes. In addition, deterministic genes directly cause the autosomal dominant AD or familial AD, such as amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2 (PS-2).
- Head injury: especially the trauma occurs repeatedly, or involves loss of consciousness; for example, head injury during collision in sport
- The risks for cardiac disease is strongly linked with the developing of AD later on. Many condition can deteriorate the heart health, such as heart disease, diabetes, stroke, high blood pressure, and high cholesterol.
- Regularly consuming tobacco and alcohol: these substances impact on the brain health.
- Mutation in non steroidal antiinflammatories (NSAIDs): impairing to encounter inflammatory pathway, producing by the intracellular oxidative stress.
- Diet: poor diet can provide enough antioxidants to our bodies, result in high inflammatory level in brain and later brain cell damaged.
It is suggested that keeping the brain healthy is the way to slow down the process of AD or not having AD by eating health diets, staying socially active, avoiding tobacco and excess alcohol, and exercising both the body and mind.