Abnormal deposition of β-protein (Aβ) is one of the most central lesions in the pathogenesis of AD. At present, the Aβ cascade reaction theory is the most recognized theory in the various hypotheses of AD pathogenesis.
Aβ is a short polypeptide with a molecular mass of approximately 4 k Da, with approximately 39–43 amino acid units. In vivo, Aβ is produced by the sequential hydrolysis of β-amyloid precursor protein (APP) by β-secretase and γ-secretase and it can be removed by hydrolysis of the Aβ enzyme. APP is an important substance that has a key role in the nervous system. It can plasticize nerve cells and regulate the ability of nerve cells to connect. It is also associated with cell growth and adhesion. Therefore, APP is ubiquitous in a variety of cells, especially in nerve cells, and it is continuously expressed and produced [15
]. When these cells undergo normal metabolism, it is easy to convert APP into Aβ. Aβ (comprising of Aβ40 and Aβ42, where Aβ42 is more prone to amyloidosis and Aβ40 is more likely to form oligomers of Aβ) has complex toxic mechanisms for neuronal cells [16
]. The formation and degradation of Aβ is in a dynamic equilibrium, so that the content of Aβ is relatively stable. When this balance is broken, the production of Aβ is excessive and the decomposition ability is insufficient, which causes a large amount of Aβ accumulation and sedimentation, thereby forming amyloid plaques (also known as SPs) and an Aβ oligomer. At present, the pathogenesis of AD can be mainly divided into two types: family type and sporadic type. Family type AD is mainly related to genes, where the coding genes of APP and γ-secretase (mainly the active central protein presenilin) mutation cause the excessive production and accumulation of Aβ, which leads to the onset of AD. The sporadic AD, in addition to the excessive production of Aβ, also decreases the decomposition efficiency of Aβ, which causes the accumulation of Aβ, leading to the onset of the disease [17
]. The former is relatively early onset and the latter is late, wherein the latter is also caused by the decline in Aβ clearance ability after aging. This is one of the reasons why AD is more common in the elderly population. With recent studies, the role of SPs in the pathogenesis of AD may not be as important as previously thought, and the Aβ oligomers produced by cellular metabolism or Aβ aggregation may have greater harm [18
]. This oligomer, that is highly toxic to the nervous system, primarily impairs the patient’s ability to learn and remember through damaging the synapse. It can cause great damage to the number of synapses in the neuronal cells and the number of synaptic receptors, which ultimately leads to nerve connection damage and reduces synaptic transmission [19
]. This ability for synaptic damage is complicated and is largely related to four signaling pathways: N-methyl-D-aspartic acid (NMDA) receptor pathway; metabotropic glutamate R5 (m Glu R5) pathway; Eph/Ephrin pathway and the c AMP-response element (CRE) pathway. At the same time, the oligomer of Aβ can also cause the tau protein to be abnormally phosphorylated [18
], resulting in further damage to the nervous system. Tau protein is a microtubule-associated protein that is mainly localized to neuronal axons under normal conditions. Its main function is to promote the formation of microtubules and maintain the stability of microtubules. Abnormal phosphorylation of tau protein affects its ability to form microtubules, while NFTs are induced to induce AD [24
]. In addition, Aβ also induces a large amount of inducible nitric oxide synthase in colloidal stellate cells by caspase. Eventually it produces a large amount of NO that damages the nerve cells. At the same time, Aβ has a strong destructive effect on the cell membrane, wherein it can insert into the cell membrane and destroy the homeostasis and integrity of the cell membrane, eventually leading to apoptosis of the nerve cells [25
]. Recent studies have shown that this cell membrane damage caused by Aβ can be inhibited by Ca ions. However, the Ca ion is a double-edged sword, which also causes an increase in membrane rupture associated with fibers grown on the surface of the lipid membranes [26
Reducing the production of Aβ and promoting the degradation of Aβ is one of the most important actions in delaying the onset of AD and treating AD.