Related Experiment Video

Updated: Jan 24, 2026

In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus
07:03

In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus

Published on: July 6, 2022

4.9K

The TREM2 T96K paradox: Stronger signaling in vitro, weaker microglia in vivo

Silvia Penati1, Marco Colonna1

  • 1Washington University in Saint Louis, School of Medicine, St Louis, MO, USA.

Neuron
|January 22, 2026
PubMed

Insights

The Alzheimer's-linked TREM2 T96K variant weakens microglial activation in female mice, contrary to prior in vitro findings. This challenges the definition of "functional gain" for TREM2 in neurodegenerative disease research.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • The TREM2 T96K variant is associated with Alzheimer's disease.
  • Previous in vitro studies suggested this variant confers a gain of function.

Purpose of the Study:

  • To investigate the in vivo effects of the TREM2 T96K variant on microglial activation in a neurodegenerative context.
  • To reassess the functional consequences of the TREM2 T96K variant in vivo.

Main Methods:

  • In vivo studies using female mice models.
  • Analysis of microglial activation and disease-associated microglial responses.

Main Results:

  • The TREM2 T96K variant unexpectedly weakened microglial activation in female mice.
  • Disease-associated microglial responses were also diminished by the variant in vivo.

Conclusions:

  • The in vivo function of the TREM2 T96K variant differs from in vitro observations.
  • The concept of
  • functional gain
  • for TREM2 needs re-evaluation in neurodegeneration.

More Related Videos

Culturing Microglia from the Neonatal and Adult Central Nervous System11:28

Culturing Microglia from the Neonatal and Adult Central Nervous System

Published on: August 9, 2013

28.8K
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion09:23

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion

Published on: October 20, 2016

14.7K

Related Concept Videos

Equivalence: In Vitro and In Vivo Bioequivalence01:17

Equivalence: In Vitro and In Vivo Bioequivalence

Body:Bioequivalence studies are crucial in evaluating whether new drugs can match an approved one regarding pharmacological effects and clinical performance. These studies test if drugs, despite different dosage forms, share identical plasma concentration-time profiles. Three types of equivalence are central to these studies: chemical, pharmaceutical, and therapeutic. Chemical equivalence indicates that two or more drug products contain identical active ingredients in equal amounts.
219
Drug Product Performance: In Vitro–In Vivo Correlation01:20

Drug Product Performance: In Vitro–In Vivo Correlation

In pharmaceutical development, it's crucial to establish a predictive in vitro–in vivo correlation (IVIVC) for two or more formulations to gain a comprehensive understanding of release properties. IVIVC reduces the need for costly in vivo studies and facilitates the establishment of meaningful dissolution specifications with significant cost savings and decreased regulatory burden. Furthermore, a meaningful IVIVC should predict Cmax and AUC within 20%, aligning with FDA guidance while...
256
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
129.9K
Paracrine Signaling01:21

Paracrine Signaling

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
59.5K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
67.9K
Synaptic Signaling01:12

Synaptic Signaling

Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
79.3K