Adiponectin, a key regulator of peripheral lipid metabolism, exhibits a positive correlation between its reduced peripheral and central levels and cognitive function in Alzheimer’s disease (AD). Previous studies suggest that adiponectin primarily crosses the blood–brain barrier to exert its neuroprotective and anti-inflammatory effects within the brain. However, the detailed mechanisms through which adiponectin improves cognitive function in AD remain unclear.
This study found that APP/PS1 mice exhibited cognitive impairment accompanied by decreased peripheral adiponectin levels and reduced adiponectin receptor 1 (AdipoR1) expression in the hippocampus (with no change in AdipoR2 expression). Knockdown of AdipoR1 in the hippocampus induced cognitive impairment and neuroinflammation in C57BL/6 J mice. Overexpression of AdipoR1 improved cognitive function, suppressed microglial activation and expression of inflammatory factors, promoted β-amyloid (Aβ) clearance, and inhibited excessive synaptic phagocytosis by microglia in AD model mice.
In vitro and in vivo experiments revealed that AdipoR1 may regulate the activation and function of hippocampal microglia in AD by modulating their autophagy to reduce abnormal lipid droplet (LD) accumulation. This study demonstrates that AdipoR1 is a highly promising therapeutic target for restoring lipid homeostasis in AD microglia, coordinating the regulation of their phagocytic function, and delaying disease progression. This is a preview of subscription content, access via your institution Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout The datasets acquired for this study are available from the corresponding author upon reasonable request.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Lancet. 2021;397:1577–90. Article CAS PubMed PubMed Central Google Scholar Alzheimer's Association. 2023 Alzheimer’s disease facts and figures.
Alzheimers Dement. 2023;19:1598–695. Liu N, Liang X, Chen Y, Xie L. Recent trends in treatment strategies for Alzheimer’s disease and the challenges: a topical advancement.
Ageing Res Rev. 2024;94:102199. McFarland KN, Chakrabarty P. Microglia in Alzheimer’s disease: a key player in the transition between homeostasis and pathogenesis.
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