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

Importance Many 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. Objective To 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 Participants This 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. Exposure Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Main Outcomes and Measures Baseline levels and longitudinal changes of global Aβ and AD-signature region tau deposition measured by PET scans. Results Among 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 Relevance The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aβ and tau deposition.