Details

Autor(en) / Beteiligte

• Kiyota, Tomomi
• Yamamoto, Masaru
• Xiong, Huangui
• Lambert, Mary P.
• Klein, William L.
• Gendelman, Howard E.
• Ransohoff, Richard M.
• Ikezu, Tsuneya
• Bush, Ashley I.

Titel

CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction

Ist Teil von

• PloS one, 2009-07, Vol.4 (7), p.e6197

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2009

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background The linkages between neuroinflammation and Alzheimer's disease (AD) pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish β-amyloid (Aβ) precursor protein mutant. Methodology/Principal Findings We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in β-amyloid precursor protein (APP) mice as early as 2–3 months of age. This is followed by increased numbers of microglia that are seen surrounding Aβ oligomers. CCL2 does not suppress Aβ degradation. Rather, CCL2 and tumor necrosis factor-α directly facilitated Aβ uptake, intracellular Aβ oligomerization, and protein secretion. Conclusions/Significance We posit that CCL2 facilitates Aβ oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Aβ seeding in the brain.