Because the occurrence of PD will seriously affect the quality of life of patients and increase the economic burden of society and families, early prevention and treatment are particularly important. Studies have shown that the level of α-syn in cerebrospinal fluid of PD patients decreased, the level of Aβ42 decreased, and the level of NF-L increased [1].Using these characteristics, the implementation of this project intends to carry out early screening for patients with PD non-motor symptoms but no PD motor symptoms, so as to achieve early intervention.
Figure 1. The distribution of Parkinson's disease incidence in age groups, SDI areas and geographic regions from 1990 to 2019. (A) was the incident number in age groups; (B) was the ASIR in SDI areas; (C) was the incident number in geographical regions. ASIR, age-standardized incidence rate; SDI, sociodemographic index[2].
PD is the second largest chronic degenerative disease of the central nervous system after Alzheimer 's disease, which is characterized by aging-dependent loss of dopaminergic neurons in the substantia nigra pars compacta and decreased dopamine levels. In the early stage of Parkinson 's disease, the patient may have pathological changes in the dorsal motor nucleus of the medullary vagus nerve and the anterior olfactory nucleus of the olfactory bulb, followed by changes in the locus coeruleus neurons and dopaminergic neurons in the pons. Therefore, olfactory and gustatory disorders may be an early clinical feature of Parkinson 's disease. In the later stage, the pathology spread to the amygdala, basal forebrain and medial temporal lobe structure. The neocortex is affected in the final stage of the disease. The pathological marker of PD is LB. LB is a neuronal inclusion body containing immunoreactive α-syn aggregates, which may also contain various neurofilament proteins and proteins involved in proteolysis, such as ubiquitin. Cell death is mainly caused by the destruction of nuclear membrane integrity and the release of α-syn aggregation of nuclear factors such as histones. Once the aggregation begins, α-syn may spread to other cells directly or indirectly. Compared with unaffected normal individuals, about 50-70 % of neurons in this region are lost when PD patients die [5-7].
Figure 2. Major Neurodegenerative diseases, their associated regions, and current therapeutic interventions. Left panel: Brain disorders are color and shown in representative areas of the brain. Right panel: current pharmacological treatments and their areas of activity within the brain. Abbreviations: Basal ganglion (BG), Brain Stem (BS), Cerebellum (Crbl), Corpus callosum (CC), Cortex (Cx), Hippocampus (Hp), Striatum (St), Substantia Nigra (SN) [3].
α-syn disease is a neurodegenerative disease characterized by abnormal accumulation of α-syn aggregates in neurons, nerve fibers or glial cells. There are three types of α-syn disease : PD, dementia with LB ( DLB ) and multiple system atrophy [8]. Studies have shown that the level of total α-syn in cerebrospinal fluid of PD patients is reduced [9], and Aβ42 can aggravate neuroinflammation and oxidative stress, leading to neurodegenerative diseases. Measuring the level of Aβ42 in cerebrospinal fluid helps to distinguish PD from AD and other neurodegenerative diseases [10]. NF-L is a neuronal structural protein, and its elevation in cerebrospinal fluid and blood reflects axonal injury and neurodegenerative diseases. NF-L is a common marker of nerve injury, which is elevated in many neurodegenerative diseases, including PD. In the early stage of PD, elevated NF-L levels can be detected [11]Therefore, all three can be used as important indicators for the diagnosis of PD.Combined with the premonitory non-motor symptoms of PD, such as olfactory dysfunction and constipation, it can provide reference for the early diagnosis and treatment of PD.
Figure3. Biomarkers for neurodegenerative diseases[4].
