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Updated: Jul 24, 2026
Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
Metabolic response of microglia to amyloid deposition during Alzheimer's disease progression in a mouse model
Kaitlyn M Marino1,2, Jayne M Squirrell3, Jenu V Chacko3
1Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Abstract:
Alzheimer's disease (AD) drives metabolic changes in the central nervous system (CNS). In AD microglia are activated and proliferate in response to amyloid β plaques. To further characterize the metabolic changes in microglia associated with plaque deposition in situ, we examined cortical tissue from 2, 4, and 8-month-old wild type and 5XFAD mice, a mouse model of plaque deposition. 5XFAD mice exhibited progressive microgliosis and plaque deposition as well as changes in microglial morphology and neuronal dystrophy. Multiphoton-based fluorescent lifetime imaging microscopy (FLIM) metabolic measurements showed that older mice had an increased amount of free NAD(P)H, indicative of a shift towards glycolysis. Interestingly in 5XFAD mice, we also found an abundant previously undescribed third fluorescence component that suggests an alternate NAD(P)H binding partner associated with pathology. This work demonstrates that FLIM in combination with other quantitative imaging methods, is a promising label-free tool for understanding the mechanisms of AD pathology.
Insights
Alzheimer's disease (AD) alters brain metabolism. Microglia in AD mice show increased glycolysis and a novel NAD(P)H binding partner, revealed by advanced imaging.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta plaques and neuroinflammation.
- Microglia, the brain's immune cells, become activated and proliferate around plaques in AD.
- Understanding microglial metabolic shifts is crucial for AD pathogenesis research.
Approach:
- Examined cortical tissue from wild-type and 5XFAD mice at various ages (2, 4, 8 months).
- Utilized multiphoton-based fluorescence lifetime imaging microscopy (FLIM) for label-free metabolic measurements.
- Analyzed microglial morphology, neuronal dystrophy, and NAD(P)H fluorescence components.
Key Points:
- 5XFAD mice displayed progressive microgliosis, plaque deposition, and neuronal damage.
- FLIM revealed increased free NAD(P)H in older mice, indicating a shift towards glycolysis.
- A novel third fluorescence component associated with NAD(P)H was identified in 5XFAD mice.
Conclusions:
- Microglial metabolic reprogramming, including glycolysis, is linked to Alzheimer's pathology.
- The newly discovered NAD(P)H binding partner may play a role in AD pathogenesis.
- FLIM is a powerful label-free tool for investigating AD mechanisms in situ.
