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P1‐160: Phosphatidylserine Exposure on Cultured Dorsal Root Ganglia Neurons From P301S TAU Mice Suggest Phagoptosis as an Extrinsic Route of Cell Death in Tauopathy
Author(s) -
Brelstaff Jack H.,
Tolkovsky Aviva,
Spillantini Maria Grazia
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.907
Subject(s) - tauopathy , phosphatidylserine , programmed cell death , microbiology and biotechnology , tau protein , biology , microglia , apoptosis , neurodegeneration , inflammation , immunology , pathology , biochemistry , medicine , alzheimer's disease , phospholipid , disease , membrane
heightened the need to better understand the relationships and interplay between the adaptive immune system and AD neuropathology. Methods:We have recently demonstrated through generation of an immune-deficient AD mouse model which lacks T-, B-, and NK-cells, that loss of these cells significantly accelerates disease pathogenesis. In addition to significant elevations in both soluble and insoluble amyloid, these ‘Rag-5xfAD’ immunodeficient mice exhibit significant alterations in neuroinflammatory phenotypes including shifts in microglial gene expression, morphology, and phagocytic capacity. To further examine the role of the peripheral immune system in AD neuropathology we performed adoptive transfer experiments of GFP bone marrow into Rag-5xfAD animals. Results:Interestingly, reconstitution of the peripheral immune system via bone marrow transplant is sufficient to reduce amyloid levels in Rag-5xfAD. Furthermore, analysis of GFP-bone marrow chimeras, established without radiation or chemotherapeutic myeloablation, has revealed significant peripheral immune cell infiltration into the brain parenchyma of 6-month-old Rag-5xfAD mice. Additional analysis and accurate identification of these infiltrating cells will yield valuable data not only on the mechanisms of infiltration but also the interactions between these peripheral immune cells and resident CNS microglia. Conclusions: Taken together, these data strongly suggest that adaptive immune cell populations play an important, albeit understudied role in restraining AD pathology.