Cellular Changes Associated with AD
The course of Alzheimer’s disease (AD) and its pathophysiology are both significantly affected by cellular alterations that are linked to the disease. Plaques can develop in the brain as a result of the accumulation of β-amyloid proteins, which are produced from amyloid precursor proteins8. Plaques can affect neuronal communication as well as the functioning of cells, which can contribute to cognitive impairment in Alzheimer’s disease.
The growth of neurofibrillary tau tangles is another characteristic of Alzheimer’s disease. Tau is a protein that helps to maintain the structural integrity of microtubules in healthy neurons8,9. This, in turn, facilitates the transport of chemicals and nutrients by neuronal microtubules. On the other hand, tau detaches from microtubules and aggregates to create tangles inside neurons when Alzheimer’s disease is present. These tau tangles disrupt the transfer of nutrients and chemicals, which ultimately results in a breakdown of synaptic communication and memory impairment.
Alzheimer’s is characterized by the widespread presence of chronic inflammation in the brain8–10. The removal of waste and toxins from the brain is the responsibility of microglia, which are the immune cells found in the brain. In contrast, Alzheimer’s disease causes microglia to become less effective at removing beta-amyloid plaques and tau tangles, which may be caused by a defect in the TREM2 gene. In Alzheimer’s disease, astrocytes, which also play a role in sweeping away trash in the brain, are unable to function properly. The buildup of microglia and astrocytes in neurons leads to the production of chemicals, which contribute to the course of Alzheimer’s disease by causing persistent inflammation and neuronal damage.
Patients with Alzheimer’s disease often have problems with the blood-brain barrier (BBB), which makes it more difficult for the brain to sweep out tau tangles and amyloid plaques and prevent glucose from entering the brain11. It is possible that these changes, together with brain shrinkage, the loss of synaptic connections, and the death of neurons, occur years before memory and cognitive difficulties become apparent.
It is essential to understand these cellular alterations to create targeted therapeutics that target the underlying mechanisms of Alzheimer’s disease (AD) and could potentially slow down or stop the progression of the disease. In the future, it is hoped that research focusing on comprehending these complicated processes may lead to more effective treatments and even prevention of Alzheimer’s disease. For example, understanding the critical pathways leading to tau phosphorylation and aggregation can foster the development of drug compounds focused on downregulating proteotoxic tau functions. Furthermore, integrating these novel therapeutics with nanotechnology may further amplify their beneficial effects by improving their bioaccumulation, enhancing biocompatibility, increasing circulation time, enabling targeting to diseased tissue, and facilitating controlled drug release.