HYBRID EVENT: You can participate in person at Baltimore, Maryland, USA or Virtually from your home or work.

10th Edition of International Conference on Neurology and Brain Disorders

October 21-23, 2024

October 21 -23, 2024 | Baltimore, Maryland, USA
INBC 2022

Zhi-Hao Liu

Speaker at Brain Disorders Conference - Zhi-Hao Liu
Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, China
Title : The impact of APOE4 genotype on the A? phagocytosis function of blood monocytes

Abstract:

Background: ApoE4 is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Previous studies have shown that innate immune dysfunction induced by ApoE4 plays an important role in brain Aβ deposition and AD. GWAS studies showed that mutations in genes related to the phagocytosis function of monocytes significantly increased the risk of AD. We previously found that decreased Aβ uptake ability of blood monocytes in AD patients was involved in the occurrence and development of AD, but the mechanism was unclear.

Objective: To analyze the correlation between ApoE4 genotype and Aβ phagocytosis function of monocyte, which may give a new insight into the mechanism of monocyte Aβ uptake dysfunction in AD

Methods: Blood monocytes of ApoE4 gene carriers (N=30) and non-carriers (N=32) from the cognitively normal population and blood monocytes of ApoE4/4 transgenic mice (N=3) and ApoE3/3 transgenic mice (N=3) were separated by ficoll density gradient centrifugation. The uptake amount of Aβ42 was detected by flow cytometry after co-culture of monocytes with Aβ42-FITC.

Results: Compared with none-ApoE4 gene carriers?Aβ42 uptake by total monocytes (CD14dim&CD14+) (p=0.0117), classical monocytes (CD14+CD16-) (p=0.0083), intermediate monocytes (CD14+CD16 +) (p=0.0457) and non-classical monocytes (CD14dimCD16+) (p=0.0230) were significantly decreased in ApoE4 gene carriers. Univariate analysis showed that the Aβ42 phagocytosis function of three subtypes of monocytes is that CD14+CD16+> CD14dimCD16+ > CD14+CD16- (P < 0.0001). In ApoE4/4 transgenic mice, the Aβ42 uptake ability of monocytes (CD115+CD11b+) was significantly decreased compared with that in ApoE3/3 transgenic mice (P=0.0234).

Conclusion: Aβ uptake ability of monocytes in cognitively normal subjects and mice carrying the ApoE4 gene is decreased than that without the ApoE4 gene, which indicates that the ApoE4 gene may be an important cause of monocyte Aβ phagocytosis dysfunction. We speculate that Aβ uptake dysfunction of ApoE4 genotype monocyte may lead to excessive Aβ deposition in the brain and participate in the occurrence and development of AD, which needs to be further investigated in the future.

What will the audience learn from your presentation?

  • Potential of blood monocyte as therapeutic targets for Alzheimer's disease
  • Effect of Apoe4 on the phagocytic function of blood monocytes

Biography:

Liu studied at the Wenzhou Medical University, Zhejiang, China, and graduated as BD in 2020. He then joined the research group of Prof. Yan-Jiang Wang at the Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China. Liu is currently studying for a master's degree in neurology at Wenzhou Medical University. He has published 2 research articles in SCI(E) journals.

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