Alzheimer’s disease has been the subject of many research studies because it is a complex disease linked to a number of genetic and environmental factors. According to Dr. Claudia Späni’s lecture, the risk for Alzheimer’s disease is often associated with the buildup of amyloid plaques. However, aging is also a major risk factor because it increases immunosenescence, or decreased immune system efficiency due to aging. An increase in age is linked to an increase in Alzheimer’s risk and decrease in immune system strength. This information adds to the complexity of the disease as an interplay between the immune system, nervous system, and other areas of the body.
Dr. Claudia Späni and her research team are interested in the influence of the immune processes in neurodegenerative disorders and aging. They focused on the relationship between the adaptive immune system and brain β-amyloidosis by using two different mouse models in two experiments. The first model was PSAPP transgenic mice, an established mouse model of Alzheimer’s disease. The second model was recombination activating gene-2 knockout (Rag2 ko) mice that lacked functional B and T lymphocytes. In the first experiment, the researchers crossbred PSAPP and Rag2 ko mice to observe congenital adaptive immune deficiency. There were decreased Aβ40 and AβA2 levels in PSAPP and Rag2 ko mice that was paralleled by an increase in Aβ42. The researchers concluded that congenital adaptive immune deficiency increases mortality in PSAPP mice. In the second experiment, the researchers studied the effects of acquired adaptive immune deficiency in PSAPP and Rag2 ko recipients. They found a five-time reduction in B and T cells and reduced 6E10-positive Aβ plaque load in Rag2 ko mice. Overall, both experiments showed decreased β-amyloid pathology and lower brain amyloid β-peptide levels in PSAPP mice. Reduced brain β-amyloid pathology was linked to enhanced microgliosis and increased phagocytosis of amyloid β-peptide aggregates.
Similarly, the Sciencedaily article “Immune system dysfunction may occur early in Alzheimer’s disease” focused on the role of inflammation and aging in Alzheimer’s disease. Researchers at the University of Colorado, University of Wisconsin, and University of California San Francisco have investigated the impact of inflammation biomarkers in blood plasma and cerebrospinal fluid (CSF) of Alzheimer’s pathology. They tested the blood and CSF samples from 173 middle-aged and older adults who did not show clinical symptoms of Alzheimer’s disease. Through enzyme-linked immunosorbent assay methods, these samples were tested for biomarkers of Alzheimer’s disease pathology and neuronal damage such as the levels of p-tau, t-tau, Aβ42,and sAPPβ. The data was statistically analyzed to determine if CSF and plasma inflammation markers could predict CSF and plasma markers of Alzheimer’s or neuronal cell damage. In the results, they found that CSF and plasma inflammation markers relay significant information about Alzheimer’s pathology and neuronal damage. Dysregulation in the innate immune system can be an early indicator event in Alzheimer’s pathology.
In both lecture and article, Alzheimer’s disease has been linked to deficiencies in the immune system. Dr. Späni’s research team found that adaptive immune deficiencies caused immunosenescence and susceptibility to infections, increasing the risk for Alzheimer’s. The article found similar effects where neuronal damage caused prolonged inflammation, which accelerated neurodegenerative processes such as Alzheimer’s. In addition, both lecture and article found that the immune system affected the level of amyloid deposition. Dr. Späni’s research team found that deficiencies in the adaptive immune system led to a reduced brain Aβ pathology, decreased Aβ levels, increased microgliosis, and clearance of Aβ aggregates. Thus, the adaptive immune system has a major role in the microglial responses to misfolded Aβ brain peptides. The article found that pro-inflammatory cascades can be deleterious to neuronal integrity depending on the amount of amyloid deposition in the brain. In other words, the immune system has a major influence on the level of amyloid β-peptides in the brain. Similarly, both lecture and article showed that aging adults have a higher risk for Alzheimer’s. Dr. Späni’s research team observed that aging negatively impacted the patient’s ability to fight infections and became a major risk factor for sporadic Alzheimer’s. The article found that aging adults were negatively affected by the systemic and central inflammation that influenced the development of Alzheimer’s-specific tau pathology and neuronal integrity. Both lecture and article showed that Alzheimer’s disease is caused by a number of factors beyond only a buildup of Aβ plaques. Both research teams aim to understand this disease on the molecular level and contribute more knowledge to improve the health and well-being of many Alzheimer’s patients.
Works Cited
IOS Press. (2018). Immune system dysfunction may occur early in Alzheimer’s disease. ScienceDaily. www.sciencedaily.com/releases/2018/02/180206115411.htm
Späni, C. et al. (2015). Reduced β-amyloid pathology in an APP transgenic mouse model of Alzheimer’s disease lacking functional B and T cells. Acta Neuropathologica Communications, 3(71), https://doi.org/10.1186/s40478-015-0251-x.
No comments:
Post a Comment