1. Academic Validation
  2. A fragment of cell adhesion molecule L1 reduces amyloid-β plaques in a mouse model of Alzheimer's disease

A fragment of cell adhesion molecule L1 reduces amyloid-β plaques in a mouse model of Alzheimer's disease

  • Cell Death Dis. 2022 Jan 10;13(1):48. doi: 10.1038/s41419-021-04348-6.
Junkai Hu 1 Stanley Li Lin 2 3 Melitta Schachner 4 5
Affiliations

Affiliations

  • 1 Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China.
  • 2 Deaprtment of Cell Biology, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China.
  • 3 Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Shantou University Medical College, Shantou, China.
  • 4 Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China. schachner@dls.rutgers.edu.
  • 5 Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, School of Arts and Sciences, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA. schachner@dls.rutgers.edu.
Abstract

Deposition of Amyloid-β (Aβ) in the brain is one of the important histopathological features of Alzheimer's disease (AD). Previously, we reported a correlation between cell adhesion molecule L1 (L1) expression and the occurrence of AD, but its relationship was unclear. Here, we report that the expression of L1 and a 70 kDa cleavage product of L1 (L1-70) was reduced in the hippocampus of AD (APPswe) mice. Interestingly, upregulation of L1-70 expression in the hippocampus of 18-month-old APPswe mice, by parabiosis involving the joining of the circulatory system of an 18-month-old APPswe mouse with a 2-month-old wild-type C57BL/6 mouse, reduced amyloid plaque deposition. Furthermore, the reduction was accompanied by the appearance of a high number of activated microglia. Mechanistically, we observed that L1-70 could combine with Topoisomerase 1 (Top1) to form a complex, L1-70/Top1, that was able to regulate expression of macrophage migration inhibitory factor (MIF), resulting in the activation of microglia and reduction of Aβ plaques. Also, transforming growth factor β1 (TGFβ-1) transferred from the blood of young wild-type C57BL/6 mice to the aged AD mice, was identified as a circulating factor that induces full-length L1 and L1-70 expression. All together, these findings suggest that L1-70 contributes to the clearance of Aβ in AD, thereby adding a novel perspective in understanding AD pathogenesis.

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