Kiel Life Science

SFB877 Seminar: 'Function and Dysfunction of microglia cells in neurodegenerative disorders'

16.01.2019 ab 17:15

Biochemie Hörsaal (Altbau), Rudolf Höber Str. 1

Proteolysis as a Regulatory Event in Pathophysiology - SFB877 Seminar

  • Gastvortrag:

    Prof. Dr. Dr. Christian Haass
    Biochemistry, LMU München

'Function and Dysfunction of microglia cells in neurodegenerative disorders'

Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional TREM2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque associated Apolipoprotein E (ApoE). Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants. Proteomic analyses and microglia depletion experiments revealed a microglial origin of plaque associated ApoE. Longitudinal amyloid small animal positron emission tomography demonstrates accelerated amyloidogenesis in TREM2 loss of function mutants at early stages, which progressed at a lower rate with aging. These findings suggest that in the absence of functional TREM2 early amyloidogenesis is accelerated due to reduced phagocytic clearance of amyloid seeds despite reduced plaque associated ApoE.

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