Polysaccharide Krestin Prevents Alzheimer’s Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-β Processing
Si-Han Chen1,2,3,6 • Chen-Yang He1,2,3 • Ying-Ying Shen1,2,3 • Gui-Hua Zeng1,2,3 • Ding-Yuan Tian1,2,3 • Yuan Cheng1,2,3 • Man-Yu Xu1,2,3 • Dong-Yu Fan1,2,3 • Cheng-Rong Tan1,2,3 • An-Yu Shi1,2,3 • Xian-Le Bu1,2,3,4 • Yan-Jiang Wang1,2,3,4,5
1 Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing 400042, China 2 The Institute of Brain and Intelligence, Third Military Medical University, Chongqing 400042, China 3 Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing 400042, China 4 State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China 5 Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 201200, China 6 Department of Neurology, Nanchong Central Hospital, The Second Clinical Medical School, North Sichuan Medical College, Nanchong 637000, China
Abstract
Deficits in the clearance of amyloid b protein (Ab) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer’s disease (AD). Impaired uptake of Ab by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Ab clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Ab uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Ab deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Ab clearance by blood monocytes and alleviating AD-like pathology.
Keywords
Alzheimer’s disease; Ab uptake; Polysaccharide krestin; Monocyte
