This week we will explore the intricacies of Alzheimer’s disease. Alzheimer’s disease is a progressive brain disorder that slowly destroys the ability of the patient to complete basic tasks. Although the prevalence of dementia and some other symptoms associated with Alzheimer’s disease increases in old age, it is not a normal part of aging.
Causes
Many factors cause Alzheimer’s disease with the most prominent one being age. The number of people afflicted nearly doubles after 65 and nearly ⅓ of all people over 85 have Alzheimer’s. Not all of the factors are known but scientists believe that it is some combination of genetics, lifestyle and environmental factors. The specific causes may be unique to each person, making it difficult for scientists to issue blanket statements of things to avoid.
However, there are a couple of genes that are closely linked to Alzheimer’s disease. For late-onset Alzheimer’s (symptoms are apparent in the mid-’60s), alleles of a gene known as APOE (apolipoprotein E) on chromosome 19 can increase your risk. APOE ɛ2 is rare and may provide protection against the disease but if you still get Alzheimer’s, it is usually later in life. APOE ɛ3 is the most common allele and neither increases nor decreases the risk for the disease. APOP ɛ4 increases the risk of Alzheimer’s disease and is associated with an earlier age of symptom onset - the more alleles you have (you can have 0,1,2) the higher your risk is.
For early-onset Alzheimer’s, a version of the disease only seen in 10% of those afflicted, symptoms can start anywhere from the early-’30s to mid -’60s. These cases are almost always linked to mutations in specific genes. Most cases are linked to inherited changes in one of three chromosomes. The three genes are amyloid precursor protein on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. These mutations are all associated with the breakdown in the formation of amyloid protein, a process that generates amyloid plaques - the hallmark of Alzheimer’s disease. This specific condition is known as early-onset familial Alzheimer's disease (FAD).
In addition, health conditions, whose prevalence also increases with age, have been potentially linked to Alzheimer’s disease. Conditions such as diabetes, heart disease, stroke, and vascular conditions are potential risk factors.
Symptoms
Physical Symptoms:
Memory impairment is one of the first symptoms of Alzheimer’s disease. Some of the early stage symptoms include poor judgment, longer time needed to complete routine tasks, repeating questions, a hard time finding things (esp. If items are found in odd places, like keys in the refrigerator), and increased anxiety.
As time goes on, the cognitive impairment of patients is increased. There are increased memory problems, and difficulty learning new things. Patients may even have hallucinations, trouble recognizing friends and family, or agitated emotions. Often times, symptoms include getting lost often even on extremely familiar routes.
For severe Alzheimer’s symptoms, patients can not take care of themselves. They lose the ability to communicate, have seizures, lose control of bodily functions, and increased the risk of infections, such as pneumonia. Aspiration pneumonia, when patients can not swallow properly, is often a cause of death for patients in this stage.
Molecular symptoms:
In Alzheimer’s disease, the brain loses a considerable amount of volume. Neurons lose connections with each other, die or stop functioning. This damage typically starts in the hippocampus, explaining the prevalence of memory symptoms at the beginning of Alzheimer’s. The progression of symptoms correlates well with the changes in the brain. The disease often targets areas in the cerebral cortex responsible for social and emotional behavior, language, reasoning, and eventually the areas necessary to perform basic functions.
Other aspects of Alzheimer’s on the molecular level include amyloid plaques, chronic inflammation and tau tangles.
Amyloid plaques are formed when an amyloid protein (specifically beta-amyloid 42) is broken down and forms toxic monomers. These monomers collect between neurons and disrupt cell communication.
Chronic inflammation is caused by the buildup of glial cells. In addition, microglia (see more here) don’t clean up excess buildup and release chemicals that cause irritation, further enhancing the inflammation.
In normal neurons, microtubules help the neuron keep its structure. Tau binds to these microtubules to help stabilize them. In Alzheimer’s disease, however, chemical changes within the cell cause tau proteins to stick to each other and not the microtubules. These connections cause tangles to form that eventually lead to blockage of the neuronal transport system harming communication between neurons.
Diagnosis
There is no one test that decisively proves that a person has Alzheimer’s or not but there are multiple factors that go into each diagnosis. Often the first step is having the patient and a close family member describe their symptoms to help the doctor classify what’s happening. If Alzheimer’s is a strong possibility, the doctor will most likely order tests that analyze neurological health (reflexes, memory, movement, coordination, etc.). Blood can be tested for other diseases such as thyroid which can cause some similar symptoms. An MRI or CT scan can show changes in the brain that can provide more evidence. More specific tests, Fluorodeoxyglucose (FDG) PET, Amyloid PET imaging, and Tau PET imaging, can test for specific molecular changes. FDG PET shows areas of the brain that are degenerating - if these areas correspond to areas known to be damaged in Alzheimer’s disease, the doctor can make their prognosis. Amyloid PET measures the number of amyloid plaques in the brain - usually only used for patients with early-onset symptoms. Tau PET is only used in research but measures the neurofibrillary tangles (tau tangles).
Treatment
There are two types of drugs that can be used to treat some of the cognitive symptoms of Alzheimer’s. Cholinesterase inhibitors boost neuronal communication by increasing levels of acetylcholine (see more here). They can also help with depression and other psychological disorders. These medications do have mild to severe symptoms such as diarrhea, sleep disorders, and loss of appetite. Memantine slows the progression of Alzheimer’s without side effects.
Since there is no cure, the only real way to help Alzheimer’s patients deal with their symptoms is through lifestyle changes.
Blog by : Lasya Kambhampati
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