Alzheimer's Disease Biochemistry - PDF

The Alzheimer’s Disease Alzheimer’s disease - A neurodegenerative disease is the most common cause of dementia. Alzheimer’sdisease is a term used to describe memory loss and other cognitive impairments that can interfere with an individual's everyday activities. It is a progress...

The Alzheimer’s Disease Alzheimer’s disease - A neurodegenerative disease is the most common cause of dementia. Alzheimer’sdisease is a term used to describe memory loss and other cognitive impairments that can interfere with an individual's everyday activities. It is a progressive disease, meaning dementia symptoms gradually worsen over several years, especially in the later stages. Although the exact cause is unknown, it is linked to abnormal protein deposits in the brain, including amyloid plaques and tau tangles. Biochemistry 1) Cholinergic Neuron Degeneration - Cholinergic neuron degeneration occurs when low acetylcholine production disrupts pre and post-synaptic interactions. - Acetylcholine, made by Choline Acetyl Transferase (CAT) from Acetyl CoA and choline helps transmit nerve signals, degraded by Acetylcholinesterase (AChE). - In Alzheimer's, reduced CAT expression results in less acetylcholine, leading to neuron atrophy. 2) Beta Amyloid Plaque Formation - β amyloid plaques form when Amyloid Precursor Protein (APP) is improperly degraded by β and γ secretase. - Insoluble 42-amino acid amyloid β peptides are produced. In Alzheimer's, overactive β-secretase causes the increased accumulation of amyloid β. - Astrocytes and microglia are overwhelmed which release Apo E., a protein responsible for neuron repair. Glutamate is released which overstimulates and kills neurons. - Plaques are formed when overproduction is not cleared fast enough, thus blocked synapses, triggering immune responses, and inflammation occurs. 3) Neurofibrillary Tangles - Neurons are supported by microtubules and are made of tubulin subunits and Tubulin Associated Unit (TAU) proteins. - To function correctly TAU must be hypophosphorylated. In Alzheimer’s, TAU becomes hyperphosphorylated, thus microtubules collapse. - The disassociated TAU proteins form neurofibrillary tangles, which disrupt neuron transport and communication. Progression/Stages a. Early-stage Alzheimer's (mild) - An individual may function independently and perform daily tasks as they are generally unaffected, though subtle signs may be noticeable - Memory lapses such as forgetting the location of familiar places, objects, or names would occur.  b. Middle-stage Alzheimer's (moderate) - The moderate stage, often the longest, can persist for several years, requiring increasingly intensive care as it progresses. - During this stage, symptoms become more pronounced, and the nerve cell damage may interfere with the person's ability to perform routine tasks independently. c. Late-stage Alzheimer's (severe) - Compared to the earlier stages, the individual’s cognitive and physical abilities decline drastically. - They experience the loss of ability to respond to the environment, and themselves. - Significant personality changes may occur with the inability to effectively communicate the pain, requiring the most intensive care and support. - This final stage can last for several years before the disease leads to complete dependency. Symptoms - The symptoms of Alzheimer’s disease develop gradually over time. In its early stages, the most common symptom individuals experience is mild memory loss. As the disease progresses, memory problems become more severe, and individuals may struggle to recognize their loved ones, recall personal information, and have language difficulties. Further, in its more advanced stages, individuals experience behavioral changes due to confusion and disorientation within them. Because of cognitive decline, they become entirely dependent on their caregivers. Treatment - As there is currently no cure for Alzheimer’s disease, finding the right treatment for patients with Alzheimer’s can be challenging because they may struggle with explaining their symptoms. There are both drug-related and non-drug related treatments available to manage symptoms of Alzheimer’s of varying stages. Medications for mild to moderate Alzheimer’s disease: - Cholinesterase inhibitors like galantamine, rivastigmine, and donepezil are used to prevent the breakdown of acetylcholine. - Effectiveness diminishes as the disease progresses. They can improve symptoms, including agitation or depression with side effects such as nausea and sleep disturbances. - Lecanemab and donanemab, target beta-amyloid plaques which helps in slowing cognitive decline. Potential risks include brain fluid buildup or bleeding. Medications for moderate to severe Alzheimer’s disease: - Memantine, an NMDA antagonist, is used to help reduce symptoms and maintain certain daily functions. It works by regulating glutamate. - Memantine can be combined with cholinesterase inhibitors since they have different mechanisms of action. Side effects may include dizziness. - Donepezil, the rivastigmine patch, and a combination of memantine and donepezil. Additionally, brexpiprazole is approved for treating agitation linked to Alzheimer’s. Non-medical Treatments: - Doctors often suggest patients with Alzheimer’s to incorporate exercise into their lifestyles to help elevate moods and maintain joint health. - Keeping up with nutrition can help prevent constipation and dehydration because patients with Alzheimer’s may forget to eat or drink or may lose interest in food. Recent Research - In 2023, the first drug to slow Alzheimer’s in its early stages, donanemab, was approved by the FDA. Promising clinical research continues for other treatments, and more studies are needed to better understand Alzheimer’s, identify risk factors, and explore prevention and new diagnostic methods.  References Alzheimer’s Association. (n.d.). Stages of Alzheimer’s. Alzheimer’s Disease and Dementia. Retrieved October 16, 2024, from https://www.alz.org/alzheimers-dementia/stages Balasa, A., Chircov, C., & Grumezescu, A. M. (n.d.). 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