Related Experiment Video

Updated: Jul 17, 2026

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
06:43

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes

Published on: February 5, 2018

Pro-inflammatory conditions promote neuronal damage mediated by Amyloid Precursor Protein and decrease its

Rommy von Bernhardi1, Gigliola Ramírez, Rodrigo Toro

  • 1Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile Marcoleta 391, Santiago, Chile. rvonb@med.puc.cl

Neurobiology of Disease
|January 24, 2007
PubMed

Insights

Inflammation impairs microglial cells' ability to clear amyloid precursor protein (APP), increasing their reactivity and neurotoxicity. This suggests impaired scavenger function in neuroinflammation is an early step in Alzheimer's disease pathogenesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Alzheimer's disease (AD) involves abnormal amyloid precursor protein (APP) processing, beta-amyloid (Abeta) aggregation, glial activation, and neuroinflammation.
  • Microglial cells, the brain's immune cells, play a critical role in AD pathogenesis.

Purpose of the Study:

  • To investigate the impact of pro-inflammatory conditions on microglial reactivity and function concerning APP.
  • To determine if inflammation exacerbates microglial-mediated neurotoxicity against APP.

Main Methods:

  • Utilized a biotinylated APP construct (biotin-APP-C-244) to study microglial uptake, degradation, and cytotoxicity.
  • Exposed microglia to APP alone, pro-inflammatory stimuli (lipopolysaccharide + interferon-gamma [LPS+IFNgamma]) alone, or in combination.
  • Assessed microglial reduction metabolism and phagocytic activity.

Main Results:

  • APP alone induced mild microglial activation, but combined with LPS+IFNgamma, it caused significant microglial cytotoxicity.
  • Pro-inflammatory conditions (LPS+IFNgamma) combined with biotin-APP-C-244 exposure led to a 75% decrease in microglial reduction metabolism.
  • While microglia readily phagocytosed biotin-APP-C-244, this process was inhibited by LPS+IFNgamma, preceding observable cell damage.

Conclusions:

  • Neuroinflammation impairs microglial scavenger function, leading to enhanced microglial reactivity towards APP.
  • This impaired clearance and heightened reactivity represent a potential early mechanism driving neurodegeneration in Alzheimer's disease.

More Related Videos

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation09:19

Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation

Published on: December 8, 2017

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Encephalitis ll: Pathophysiology01:26

Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.