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.