Alzheimer's Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities
Chapter 2: The Genetic and Biochemical Basis of Alzheimer's Disease
Published:04 Jan 2022
Kottapalli Srividya, Aamir Nazir, 2022. "The Genetic and Biochemical Basis of Alzheimer's Disease", Alzheimer's Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities, Thimmaiah Govindaraju
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As healthy aging gets disrupted by varied causes, neurodegenerative diseases such as Alzheimer's disease (AD) pose a potent threat to the well-being of the elderly. The human brain is a magnificent circuit ever-wired by evolution with a hundred billion neurons, and their partner cells wiring the center for memory and cognition. As these intricate returns are conducted by synapses and other signaling processes in unison, this maintains the nervous system's homeostasis. When this balance goes awry because of β-Amyloid plaques and fibrillar tau protein tangles, the neuronal connectivity is hampered.
Pathologies that feature AD are the aggregation of the β-Amyloid forming plaques in the brain and twisted filaments of the tau protein resulting in formation of fibrillary tangles inside neurons. These accumulations of β-Amyloid plaques result in defective clearance, which in return contributes to the extensive damage and death of neurons by the consequent outcome of damaged neuronal communication at the synapses.1 On the other hand, Tau protein forms fibrillary tangles that block the transport of essential nutrition. Although the complete schema of pathophysiology is not marked out, whether β-Amyloid aggregation affects tau or it is first tau fibril formation that affects protein aggregation is not well deciphered. Apart from structural defects, other brain changes engage inflammation and atrophy.2 The presence of lethal aggregates of β-Amyloid and tau proteins triggers the defense system, i.e. neuronal immune system cells. These cells, called microglia, try to remove the undesirable protein aggregates as well as prevent the widespread of debris from the dead and dying cells. Persistent inflammation may set in when the microglia cannot keep up with all those pressures. This results in atrophy of the brain as well as cell loss.3 Healthy brain function is further compromised in AD as these different physiological deficits hamper metabolism. These changes result in the death of neurons and prolific damage to the brain. Alzheimer's is a slow yet progressive brain ailment that begins many years before symptoms emerge. Based on the onset of AD, it can be either early-onset of AD (EOAD) or late-onset of AD (LOAD). Fittingly, these symptoms include trouble in remembering recent conversations, names, or events that deteriorate to apathy and depression. As the condition progresses, these symptoms step up to impaired communication, disorientation, blurring, poor decision making, behavioral shifts and ultimately, difficulty in mundane activities such as speaking, swallowing, and walking.4