The Study Of Social Networks And Cerebrospinal Fluid Biomarkers Of Alzheimer’s Disease Pathology

Background:With complex aetiological profiles underpinned by both major genetic culprits and indispensable environmental contributors,Alzheimer’s disease（AD）is one of the most common dementia and neurodegenerative diseases characterized by progressive cognitive impairment and behavioral impairment,often occurring in middle-aged and elderly people.At present,there is no effective treatment that can prevent and delay the occurrence of the disease worldwide.The number of people living with AD continues to increase and is about to reach 152 million in 2050.Dementia has become one of the major threats to human health.A growing body of evidence-based studies suggests that AD is preventable using effective and reasonable methods.Identifying and controlling risk factors effectively and using of protective factors rationally can significantly reduce the occurrence and progression of AD.Although social networks are deemed as moderators of incident AD,no research has conclusively assessed their associations with cerebrospinal fluid（CSF）AD biomarkers in humans at home and abroad.Objective:We aimed to investigate associations of social networks with CSF AD biomarkers during early stage of AD in cognitively intact older adults.Methods:We studied participants from the Chinese Alzheimer’s disease Biomarker and Lifestyle study with available CSFβ-amyloid(β-amyloid 1-42[Aβ_1-42]andβ-amyloid 1-40[Aβ_1-40])and tau proteins（total-tau[T-tau]and phosphorylated-tau[P-tau]）data.The established social network scores reflected an individual’s social network closeness.A series of multiple linear regression analysis were used to examine the potential associations between social network and CSF biomarkers and these ratios,controlling for age,sex,education,APOE-ε4 status,MMSE scores.Subgroup analyses were also conducted according to APOE-ε4 carrier status and cognitive status to further explore the association.Results:Data were analyzed from 886 cognitively intact individuals aged 61.91 years（SD=10.51）,including 295 preclinical AD participants and 591 healthy controls.The proportion of males was 58.92%,and the proportion of APOE-ε4 carriers was 15.44%.Social networks were mostly associated with CSF indicators of AD multi-pathologies(low P-tau/Aβ_1-42and T-tau/Aβ_1-42and high Aβ_1-42/Aβ_1-40).Significant differences of genetic and cognitive status were observed for CSF indicators,in which associations of social network scores with CSF P-tau and indicators of multi-pathologies appeared stronger in APOE-ε4 carriers（vs.non-carriers）and participants with subjective cognitive decline（vs.controls）,respectively.Alternatively,more pronounced associations for CSF T-tau（β=-0.005,P<0.001）,Aβ_1-42/Aβ_1-40（β=0.481,P=0.001）,and T-tau/Aβ_1-42（β=-0.047,P<0.001）were noted in participants during preclinical stage of AD but not in healthy controls.Conclusion:These findings report social network subcomponents and comprehensive social network index in the associations with alterations of CSF AD biomarkers during cognitive unimpaired stage and presents evidence for social networks as a modifiable lifestyle,probably affecting the metabolisms of multiple core pathologies of AD,especially among those at-risk populations,such as APOE-ε4 carriers and participants with subjective cognitive decline.This work will inform future research into the neurobiology of social networks and other socio-behavioral or socio-psychological factors thereby promoting the intervention studies in AD.