Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| [b] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Correspondence:
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Correspondence to: Jin-Tai Yu, MD, PhD, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: yu-jintai@163.com; Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao, China. E-mail: dr.tanlan@163.com.
Abstract: Background:Existed evidence suggests that midlife obesity increases the risk of Alzheimer’s disease (AD), while there is an inverse association between AD and obesity in late life. However, the underlying metabolic changes of AD pathological proteins attributed to obesity in two life stages were not clear. Objective:To investigate the associations of obesity types and obesity indices with AD biomarkers in cerebrospinal fluid (CSF) in different life stages. Methods:We recruited 1,051 cognitively normal individuals (61.94±10.29 years, 59.66%male) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study with CSF detections for amyloid-β 42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau). We utilized body mass index, waist circumference, waist-to-height ratio, and metabolic risk factors to determine human obesity types. Multiple linear models and interaction analyses were run to assess the impacts of obesity on AD biomarkers. Results:The metabolically unhealthy obesity or healthy obesity might exert a reduced tau pathology burden (p < 0.05). Individuals with overweight, general obesity, and central obesity presented lower levels of tau-related proteins in CSF than normal controls (p < 0.05). Specially, for late-life individuals, higher levels of obesity indices were associated with a lower load of tau pathology as measured by CSF T-tau and T-tau/Aβ42 (p < 0.05). No similar significant associations were observed in midlife. Conclusion:Collectively, late-life general and central obesity seems to be associated with the reduced load of tau pathology, which further consolidates the favorable influence of obesity in specific life courses for AD prevention.
Keywords: Alzheimer’s disease, biomarkers, body mass index, cerebrospinal fluid, obesity, waist circumference, waist-to-height ratio
