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P2‐196: MICROGLIAL MOTILITY IN ALZHEIMER'S DISEASE AND AFTER Aβ42 IMMUNOTHERAPY: A HUMAN POSTMORTEM STUDY
Author(s) -
Franco-Bocanegra Diana K.,
George Bethany E.,
Lau Laurie C.,
Holmes Clive,
Nicoll James A.R.,
Boche Delphine
Publication year - 2019
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.2019.06.2603
Subject(s) - microglia , motility , biology , population , immunology , immunotherapy , alzheimer's disease , inflammation , pathology , immune system , microbiology and biotechnology , disease , medicine , environmental health
Background: The retina of patients with Alzheimer’s disease (AD) display several abnormalities, including the presence of Ab deposits, tauopathy, and retinal ganglion cell (RGC) degeneration. Although inflammatory responses are tightly correlated with AD brain pathology, the processes in the retina are underexplored. Methods: Here, we study retinal pathology including amyloidosis, gliosis, and analysis of RGCs in mild cognitively impaired (MCI) and AD patients compared to ageand sexmatched controls. We quantified amyloid beta (Ab) load (4G8 and 12F4) as well as macroand micro-gliosis (M€uller glia, GFAP, s100b, Iba1) in defined retinal layers and sub-geometrical regions in MCI and AD patients versus matched controls. Results: We found a wide range of pathological changes in retinal tissues isolated from MCI and AD patients as compared to controls. Ab deposits were more abundant in inner retinal layers with substantial 4to 10fold increases in total Ab and especially Ab42-specific burden in peripheral regions in early stages of AD patients as compared to controls. We observed that RGCs express APP and are a major cellular component of Ab accumulation in the retina. Importantly, increasing retinal Ab burden was tightly associated with gliosis, including reactive astrocytes and activated microglia. The greatest observed change was in astrogliosis in far peripheral regions with a 3.3-fold change in AD compared to controls. Astrocytes were not only in inner retina, they were propagating into outer regions of the MCI and AD retina. M€uller glias were also activated by 1.7fold in AD retina. Peripheral areas of the retina seem to be more sensitive to damage than central areas. Our results show that retinal amyloid burden can predict plaque load in the brain. Conclusions: Taken together, our findings suggest that early and progressive pathological accumulation of retinal Ab is closely associated with inflammation in the retina of AD patients. These studies support non-invasive retinal imaging as a biomarker for early detection and monitoring AD.