Related Experiment Video

Updated: Jun 25, 2026

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
10:52

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques

Published on: June 1, 2016

11.8K

Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation

Michael Ewers1,2, Gloria Biechele3, Marc Suárez-Calvet4,5,6

  • 1Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University (LMU), Munich, Germany.

EMBO Molecular Medicine
|August 14, 2020
PubMed

Insights

Increased microglia activation, measured by CSF sTREM2 or PET scans, appears to protect against amyloid-beta accumulation in Alzheimer's disease (AD). This suggests a beneficial role for these immune responses in AD progression.

Area of Science:

  • Neuroscience
  • Immunology
  • Neurology

Background:

  • Microglia activation is a key brain immune response in Alzheimer's disease (AD), linked to amyloid plaques.
  • Biomarkers like soluble TREM2 (sTREM2) in CSF and microglia PET scans are elevated in AD.
  • The relationship between increased microglia activation and reduced amyloid-beta (Aβ) accumulation is not fully understood.

Purpose of the Study:

  • To investigate whether elevated microglia activation biomarkers predict reduced amyloid-beta accumulation in Alzheimer's disease.
  • To explore the association between cerebrospinal fluid sTREM2 levels and longitudinal changes in amyloid PET.
  • To examine the correlation between microglia PET imaging and amyloid PET progression in a mouse model of amyloidosis.

Main Methods:

  • Human study: Measured CSF sTREM2 to predict longitudinal amyloid PET changes and cross-sectional tau PET in non-demented and demented individuals.
  • Animal study: Utilized the AppNL-GF mouse model to assess baseline 18F-GE180 microglia PET and longitudinal amyloid PET.
  • Controlled for confounding pathologies in the mouse model to isolate the microglia-amyloid relationship.

Main Results:

  • In humans, higher baseline CSF sTREM2 levels correlated with attenuated increases in amyloid PET over two years and lower tau PET.
  • In mice, higher baseline microglia PET at 5 months was associated with a slower rate of amyloid PET increase between 5 and 10 months.
  • These findings demonstrate a consistent protective association between heightened microglia activation and reduced subsequent amyloid accumulation.

Conclusions:

  • Elevated microglia activation, indicated by CSF sTREM2 or microglia PET, demonstrates a protective effect against subsequent amyloid accumulation.
  • This suggests that targeting microglia activation could be a potential therapeutic strategy for Alzheimer's disease.
  • The study provides translational evidence from human and animal models supporting a beneficial role for microglia in mitigating amyloid pathology.
Keywords:
TREM2beta-amyloid accumulationmicrogliaprotectivetau

More Related Videos

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease09:33

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Published on: December 26, 2016

8.3K
A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of Aβ and Tau Levels in Rhesus Monkey Cerebrospinal Fluid06:22

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of Aβ and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

Published on: September 3, 2021

3.9K

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...