Study on the Relationship Between Peripheral Blood miRNA and Risk and Severity of Alzheimer's Disease

Alzheimer's Disease, AD is a type of neurofibrillary tangles formed by the deposition of beta amyloid proteins within the nervous system cells and excessive phosphorylation of extracellular Tau proteins, NFTs are the main pathological features of central nervous system degeneration, also known as senile dementia. In addition, synaptic plasticity damage and neuroinflammation also play important roles in the progression of AD. Neurosynapses are the sites where neurons interact with each other in terms of function, and are also crucial for neuronal information transmission and communication. Synapses are the fundamental units in the brain, and synaptic activity can stimulate the maturation of mushroom like dendritic spines and form new synapses, enabling synaptic strength to adapt to changes in the internal and external environment, thereby playing an important role in learning and memory. Previous studies have shown that synaptic activity interruption and synaptic loss can already be detected in the AD brain, especially in the early stages. Multiple studies have shown a higher correlation between synaptic disorders characterized by synaptic loss and decreased synaptic activity and cognitive impairment in Alzheimer's disease compared to age-related plaques and neurofibrillary tangles. Therefore, understanding the potential mechanisms of synaptic disorders will contribute to the development of early treatment strategies for AD. MicroRNAs (miRNAs) are a type of small non coding RNA with a length of approximately 22 nucleotides. Their main function is to silence target genes at the post transcriptional level and inhibit the translation process of their proteins. MiRNAs are involved in many physiological processes and pathological pathways, including development, tumorigenesis, and heart disease. Recently, people have also studied the abnormal regulatory role of miRNAs in AD synaptic disorders. Some miRNAs enriched in the brain, such as miR-124, MiR-132 is abnormally expressed in the AD brain, mediating synaptic plasticity damage. However, most of the miRNAs mentioned above are not directly related to synaptic activity, and their regulation of AD synaptic damage is likely to be a broad-spectrum effect. At present, there are 12 miRNAs closely related to synaptic plasticity that have been identified. By detecting changes in miRNAs closely related to synaptic plasticity in peripheral blood of AD patients and healthy volunteers, and exploring their relationship with the severity of AD lesions, it may provide new directions for early diagnosis of AD. The purpose of this study is to: (1) detect the expression levels of miRNAs closely related to synaptic plasticity in the peripheral blood of healthy volunteers and AD patients, and identify the miRNAs with the greatest differences; (2) Analyze the relationship between the expression levels of the aforementioned miRNAs in the peripheral blood of AD patients and the severity of the disease; (3) Analyze the relationship between the expression levels of the aforementioned miRNAs in the peripheral blood of AD patients and the commonly used neuropsychiatric scale scores. We plan to clarify the changes in peripheral blood miRNAs and their relationship with the severity of AD through case-control studies, in order to provide new directions for early diagnosis of AD.