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O2‐13‐01: INCIDENCE OF CEREBRAL MICROBLEEDS AND AMYLOID BURDEN: THE MAYO CLINIC STUDY OF AGING
Author(s) -
Radford Jonathan Graff,
Vemuri Prashanthi,
Rabinstein Alejandro,
Przybelski Scott A.,
Lesnick Timothy G.,
Flemming Kelly,
Brown Robert D.,
Knopman David S.,
Roberts Rosebud O.,
Mielke Michelle M.,
Kremers Walter K.,
Jones David T.,
Huston John,
Lowe Val J.,
Petersen Ronald C.,
Jack Clifford R.,
Kantarci Kejal
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.2018.06.2712
Subject(s) - cerebral amyloid angiopathy , medicine , pittsburgh compound b , incidence (geometry) , odds ratio , confidence interval , logistic regression , magnetic resonance imaging , cardiology , alzheimer's disease , radiology , dementia , disease , physics , optics
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.