Alzheimer’s Disease

Alzheimer’s Disease is one of the major neurodegenerative diseases that affect the brain tissue. It is the most common reason for dementia. In the world populations, almost 5 million cases are reported each year and this incidence is rising by time unfortunately. Because of the loss of neuron and brain tissue, the mental and cognitive functions gradually decrease. There is still no treatment, and the current medications just reduce symptom’s progression and aim to make life time as long as they can. Although the exact mechanism is still unclear since the increase of multidisciplinary studies, our knowledge about Alzheimer’s genetic and pathophysiologic mechanisms is increasing day by day. According to recent studies, there are two major mechanisms that play a role in Alzheimer’s pathology. Beta-Amyloid plaques (Senile plaques) and aggregated Tau proteins (Neurofibrillary tangles).

            Beta-Amyloid proteins occur from cleavage of the APP (Amyloid Precursor Protein) that is a transmembrane protein which the physiological role is not exact yet. As a result of cleavage of the APP by an enzyme complex called beta secretase, beta-amyloid monomers start to accumulate in extracellular regions. Monomers make oligomers and the oligomers finally get together and make the senile plaques. Due to senile plaques, the signal transduction between cells is interrupted. By this way the neurons undergo a fast apoptotic stage and brain tissue goes to necrosis.

Tau is a protein where located at the microtubules and holding together the microtubules which provide signal and nutrients transportation inside of neurons as like the other cells. Explanation about the tau protein mechanism is still unclear but it is believed that the major reason for accumulation of tau protein is extracellular beta-amyloid deposits. Major acceptance is that amyloid deposits stimulate some biochemical pathways inside of cells and result in increasing kinase activity, the tau proteins become hyperphosphorylated and lose their affinity to microtubules. Due to changing structure of tau proteins, they start to seperate from microtubules and make filaments inside of cells called neurofibrillary tangles. Because there are no structures that make stabilization and holding together microtubules, it starts to loose and dissipate. Therefore, the cells could not transport the signals through cells, neuron’s apoptotic stage and clinical course of disease become faster.

There are several genetic factors that play important role in Alzheimer’s disease but the most common and modifiable gene is APOE (Apolipoprotein E). As known the APO’s major role is transportation of lipids inside of the body. It is the major cholesterol carrier in the brain. APOE has three allele as e2, e3, e4 and among of these isoform, e4 has biggest risk for Alzheimer Disease. According to recent researches, it is believed that the APOE increases clearance of beta-amyloids but e4 alleles have lowest affinity to beta-amyloids. Thus e4 isoform of APOE, has lowest clearance of beta-amyloids. One e4 allele increases the risk of disease at 3 fold, two alleles increase the risk at 9-12 fold but still in a large number of reported cases that even some of them have two e4 alleles, did not develop the disease. Major cause of that situation is shown that long term low cholesterol levels. Because the low cholesterol level mean that low APOE workload, and low APOE workload mean that low APOE gene expression. So if you even have two e4 allele of APOE gene, a lifestyle with low cholesterol levels suppresses the APOE gene expression and in this way risk of Alzheimer Disease is significantly decreases.

May you cannot change your genes, but you can change your cholesterol levels. With a healthy diet and an active life, there is no such thing that you cannot succeed.

For a healthy and quality life, do not neglect to have your check-ups regularly.

“Page content is for informational purposes only. Please contact us for diagnosis and treatment. “

Dr. Emre Seyhan