Relationship Between Sleep Disorder And ApoE Gene Polymorphisms And Lp-PLA₂ In Patients With Alzheimer's Disease

Background and ObjectiveAlzheimer's disease?AD?is one of the most common diseases in the elderly which causes the elderly to lose their ability to work in daily life,and it is also the fifth cause of death of the elderly.This is a huge problem facing the health and economic development of the world society.It is a degenerative disease of the central nervous system characterized by progressive cognitive impairment and behavioral disorders.Clinical manifestations include impaired memory function,aphasia,apraxia,impaired visual space function,decreased executive power,computational power,and changes in personality and behavior.At present,the number of AD patients in China's elderly population has exceeded 6 million.It is expected that by 2050 the number of AD patients will exceed 20 million people,which is the largest number of AD patients and the fastest growing prevalence.It caused great suffering to the patients and aggravated family stress and social medical care and care burden.Sleep is one of the important biological functions of humans.Sleep-wake process relies on sleep-related nuclei such as the brain stem,hypothalamus,and basal forebrain to form a neuromodulation circuit and gamma-aminobutyric acid?GABA?and acetylcholine?ACh?.The regulation of neurotransmitters such as 5-hydroxytryptamine?5-HT?.In recent years,the high incidence of sleep abnormalities in AD patients has receivedextensive attention.According to research statistics,25-66%of AD patientsmay show some type of sleep abnormality during the course of the disease.Although it was previously thought that sleep disorders were associated only with severe degeneration of neurological function,recent studies have found that sleep abnormalities can occur early in AD and canexacerbate the severity of cognitive decline.Apolipoprotein E?ApoE?,as an important factor regulating the metabolism of body lipids and lipoproteins,affecting blood lipid levels and atherosclerosis,is also involved in the growth of nerve cells and the repair process after injury.The ApoE?4 allele can affect the folding process of APP and induce the increase of A?production.In recent years,studies have shown that A?may affect sleep patterns of AD patients through abnormal deposition in sleep-regulating areas and neuroinflammation mechanisms,and play a role that can not be ignored in the course of disease.Lipoprotein-associated phospholipid A2?Lp-PLA2?is one of the core enzymes of inflammatory reactions and participates in the synthesis of inflammatory mediators.Studies have reported that PLA₂ is not only an independent risk factor for coronary heart disease and stroke.In addition to LDL and vascular factors,PLA₂ is closely related to the occurrence of dementia because of its interaction with A?.Unlike sleep disorders in non-dementia patients,sleep abnormalities in AD patients continue to worsen with the progression of the disease and can exacerbate the decline in cognitive function.It has been reported that effective intervention in early sleep disorders in AD patients can delay AD.Progress of the disease,therefore,to understand the mechanism of sleep disorders in AD patients can guide clinical more effective treatment.At present,there are few studies on the effects of ApoE gene and PLA₂ on sleep in AD patients.In this paper,through the study of ApoE gene polymorphism and plasma Lp-PLA₂,the possible effects of ApoE gene and PLA₂ on sleep disorders in AD patients are discussed.Learn more about the mechanism of AD sleep abnormalities.Methods62 AD patients and 26 healthy controls were selected and divided into two groups according to whether they were associated with sleep abnormalities.Sleep abnormalities?AD-1 group?and no sleep disorder group?AD-2 group?were tested for ApoE polymorphism and Serum Lp-PLA₂ and other serological indicators,Two groups of patients were assessed with the Mini Mental Status Checklist?MMSE?,the Pittsburgh Sleep Quality Index?PSQI?,and the Epsise Sleepiness Scale?ESS?to evaluate cognitive and sleep status in both groups.Results1.The highest rates of PSQI subscales in AD patients with sleep disorders were sleep efficiency?56.3%?and daytime dysfunction?50.0%?,and all of them were mildly damaged;2.The evaluation results of the ESS scale showed that the incidence of sleepiness in AD patients was 59.4%,mainly in mildly impaired.3.The ApoE?3/4 and?2/4 genotypes in the AD-1 group were significantly higher than those in the healthy control group?P<0.05?,and the ApoE?3/4genotype was significantly higher than that in the AD-2 group?P<0.05?.4.The frequency of ApoE?4 allele in AD-1 group was significantly higher than that in healthy control group?P<0.05?;5.In AD patients with ApoE?4 allele,the total score of MMSE was lower than that of patients without ApoE?4 allele,and the levels of Lp-PLA2,LDL-C,and IL-6 were significantly higher than those of patients without ApoE?4 allele?P<0.05?.ConclusionsSleep disorders in AD patients were mainly manifested as reduced sleep efficiency and daytime dysfunction,and the incidence of sleepiness was high.;ApoE gene polymorphisms may be involved in the decline of cognitive function and sleep abnormalities in AD patients;plasma Lp-PLA2 may be involved in the development of sleep disorders.