{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T10:48:52Z","timestamp":1793789332964,"version":"4.6.1"},"reference-count":98,"publisher":"Society for Neuroscience","issue":"9","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":215,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2020,2,26]]},"abstract":"<jats:p>\n                    <jats:italic>TREM2<\/jats:italic>\n                    is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of\n                    <jats:italic>Trem2<\/jats:italic>\n                    in a mouse model of \u03b2-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking\n                    <jats:italic>Trem2<\/jats:italic>\n                    (PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    ) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    mice, with\n                    <jats:italic>Trem2<\/jats:italic>\n                    -deficient microglia showing compromised expression of proliferation\/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    females at 6\u20137 months; but by 12 or 19\u201322 months of age, it was notably diminished in female and male PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    brains, and the A\u03b242:A\u03b240 ratio was elevated. The amount of soluble, fibrillar A\u03b2 oligomers also increased in PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    hippocampi. Associated with these changes, axonal dystrophy was exacerbated from 6 to 7 months onward in PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    mice, notwithstanding the reduced plaque load at later ages. PS2APP;Trem2\n                    <jats:sup>ko<\/jats:sup>\n                    mice also exhibited more dendritic spine loss around plaque and more neurofilament light chain in CSF. Thus, aggravated neuritic dystrophy is a more consistent outcome of\n                    <jats:italic>Trem2<\/jats:italic>\n                    deficiency than amyloid plaque load, suggesting that the microglial packing of A\u03b2 into dense plaque is an important neuroprotective activity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Genetic studies indicate that\n                    <jats:italic>TREM2<\/jats:italic>\n                    gene mutations confer increased Alzheimer's disease (AD) risk. We studied the effects of\n                    <jats:italic>Trem2<\/jats:italic>\n                    deletion in the PS2APP mouse AD model, in which overproduction of A\u03b2 peptide leads to amyloid plaque formation and associated neuritic dystrophy. Interestingly, neuritic dystrophies were intensified in the brains of\n                    <jats:italic>Trem2<\/jats:italic>\n                    -deficient mice, despite these mice displaying reduced plaque accumulation at later ages (12\u201322 months). Microglial clustering around plaques was impaired, plaques were more diffuse, and the A\u03b242:A\u03b240 ratio and amount of soluble, fibrillar A\u03b2 oligomers were elevated in\n                    <jats:italic>Trem2<\/jats:italic>\n                    -deficient brains. These results suggest that the Trem2-dependent compaction of A\u03b2 into dense plaques is a protective microglial activity, limiting the exposure of neurons to toxic A\u03b2 species.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1871-19.2019","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T17:49:23Z","timestamp":1579888163000},"page":"1956-1974","source":"Crossref","is-referenced-by-count":180,"title":["Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the A\u03b242:A\u03b240 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model"],"prefix":"10.1523","volume":"40","author":[{"given":"William 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