A review of Alzheimer’s pathophysiology and treatment
Alzheimer’s disease is the most common cause of dementia and is associated with high mortality in the elderly. Today, 47 million people worldwide are suffering from this disease, 13% of people over 65 years old and 45% of people over 85 years old are in this group. It is predicted that by 2050, one person will be diagnosed with this disease every 33 seconds and the total number of new cases will reach one million people every year.
Pathological features of Alzheimer’s disease
Although the cause of Alzheimer’s disease has not been fully identified, the amyloid cascade hypothesis seems to be the main cause of this disease. It is believed that the imbalance between the production and clearance of amyloid beta proteins in the brain and the subsequent disruption of synaptic function and degeneration of neurons is the main cause of progressive and irreversible memory impairment and affects the power of speech, personality and cognition. This hypothesis is briefly shown in Figure 1.
Amyloid plaques are composed of the accumulation of amyloid beta proteins, which are derived from a parent protein called amyloid precursor protein [1]. Three types of secretase enzymes (alpha, beta and gamma) break down the amyloid precursor protein into soluble components. In case of inappropriate breakdown of this protein by beta and gamma secretase enzymes, insoluble beta amyloid proteins are formed, which accumulate in the brain and lead to the formation of amyloid plaques, brain toxicity and cell death. Intraneuronal interwoven filaments consist of filaments containing the phosphorylated form of tau proteins [2].
Tau proteins naturally contain phosphate molecules. In Alzheimer’s disease, these proteins are excessively phosphorylated and this leads to their twisting around each other and the formation of insoluble tangles, and as a result of this, the presence of macrophages and mononuclear cells in the cerebral cortex and the activation of microglia in the parenchyma. Dementia and atrophy of the frontal-temporal cortex[3] follow. Figure 2 shows this pathological process in general.
Although experts in neuropathology believe that amyloid plaques and inter-neuronal interwoven fibers are the most important cause of Alzheimer’s disease, there are other predisposing factors that will be discussed in general below;
- In some families, genetic mechanisms have been identified for the occurrence of this disease, among which we can refer to the e-4 allele of apolipoprotein E[4]. Apolipoprotein E has an important role in breaking down and cleaning the amyloid precursor protein and it seems that e-4 allele carriers do not have the necessary ability to clean the products resulting from the breakdown of this main protein and as a result of this, the production and accumulation of beta proteins in the body increases.
- Nerve inflammation is an important factor as a cause of disease as well as a result of disease. Probably, the production of plaques and interwoven threads occurs to some extent in connection with the inflammatory process caused by aging. The production of plaques and interwoven threads causes inflammation and accelerates the formation of subsequent plaques and deterioration of cognition.
