Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults
Authors: Lee Seunghoon , Byun Min Soo , Yi Dahyun , Ahn Hyejin , Jung Gijung , Jung Joon Hyung , Chang Yoon Young , Kim Kyungtae , Choi Hyeji , Choi Jeongmin , Lee Jun-Young , Kang Koung Mi , Sohn Chul-Ho , Lee Yun-Sang , Kim Yu Kyeong , Lee Dong Young ,   Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease (KBASE) Research Group, Mook Inhee , Choi Murim , Lee Yu Jin , Hahn Seokyung , Kim Hyun Jung , Chang Mun Young , Han Na Young , Pae Jisoo , Park Hansoo , Kim Jee Wook , Lee Jong-Min , Lee Dong Woo , Sohn Bo Kyung , Moon Seok Woo , Baek Hyewon , Kim Yoon-Keun , Kim Jong-Won , Ryu Seung-Ho , Kim Shin Gyeom , Woo Jong Inn , Kim Sang Eun , Cheon Gi Jeong , Kang Koung Mi , Park Jee-Eun , Yu Hyeong Gon , Choi Hyo Jung , choe Young Min , Kim Kwangsoo , Jeon So Yeon , Kim Woo Jin , Ko Kang , Lee Jun Ho , Park Sung Wook , Jung Gijung , Joung Haejung , Ann HyeJin , Lee Han Na , Jung Joon Hyung , Byeon Gihwan , Sung Kiyoung , Han Dong Kyun , Han Seung Min , Kim Min Jung , Kim Min Jae , Kong Nayeong , Park Seo Hee , Kim Mimi , Cha Woojin , Yeom Hyeryeon , Chang Yoon Young , Keum Musung , Kim Min Jeong , Kim Donghee , Kim Kyungtae , Choi Jeongmin , Choi Hye Ji , Bae Han Sol , Woo Dohyun , Ha Seunghyuk 
Published: May 2024

ImportanceMany epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood.ObjectiveTo examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aβ) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults.Design, Setting, and ParticipantsThis was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aβ deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aβ deposition were included.ExposurePlasma leptin levels as assessed by enzyme-linked immunosorbent assay.Main Outcomes and MeasuresBaseline levels and longitudinal changes of global Aβ and AD-signature region tau deposition measured by PET scans.ResultsAmong the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aβ deposition (β = −0.04; 95% CI, −0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (β = −0.02; 95% CI, −0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (β = −0.06; 95% CI, −0.11 to −0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aβ deposition (β = 0.006; 95% CI, 0.00-0.02; P = .27).Conclusions and RelevanceThe present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aβ and tau deposition.