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O2‐12‐06: NEUROPATHOLOGICAL FINDINGS DRIVEN BY AN APOEε4 LIVER PHENOTYPE
Author(s) -
Patra Kalicharan,
Giannisis Andreas,
Nielsen Henrietta M.
Publication year - 2018
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.2018.06.2711
Subject(s) - apolipoprotein e , neuroinflammation , endocrinology , neuropathology , medicine , phenotype , biology , alpha synuclein , pathology , inflammation , disease , parkinson's disease , gene , biochemistry
performance on memory tasks before and after treatment with antibodies that reduce the incidence of capillary plugging. Results:About 1.5% of cortical capillaries were transiently stalled in AD mice, leading to an overall reduction in cerebral blood flow (CBF). These stalls were released using an antibody against the neutrophil cell surface protein Ly6G, resulting in an immediate w25% increase in CBF and an immediate improvement in performance on short-term memory tasks. Mice treated with an isotype control antibody showed no improvement in CBF or memory performance. In a second set of experiments we deterimend that reducing capillary stalls and increasing CBF led to improved cognitive performance in mice with relatively advanced AD pathology (17 month old APP/PS1 mice, first cognitive impacts detectible at 8 months). Conclusions: In this study we uncovered leukocyte adhesion in brain capillaries as a mechanism contributing to reduced CBF in AD mouse models and showed that blocking this adhesion leads to immediate cognitive benefits even in advanced stages of disease development.