Lactate deficit in an Alzheimer disease mouse model: the relationship with neuronal damage
Abstract
Cerebral energy metabolism in Alzheimer disease (AD) has recently been given increasing attention. This study focuses on the alterations of cerebral lactate metabolism in the double-transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD. Immunofluorescence staining and Western blotting analysis were used to identify the alterations of lactate content and lactate transporters (MCT1, MCT2, MCT4) in APP/PS1 mouse brains, which display amyloid beta plaques, reduced amounts of neurons and oligodendrocytes, and increased quantity of astrocytes. We found that lactate content and expressions of cerebral MCT1, MCT2, and MCT4 were decreased in APP/PS1 mice. In particular, lactate dehydrogenase A (LDHA) and B (LDHB) were reduced in neurons with increased ratios of LDHA and LDHB. This study suggests that the decreases of cerebral lactate content and lactate transporters may lead to the blockage of lactate transport from glia to neurons, resulting in neuronal lactate deficit. The increased ratio of neuronal LDHA and LDHB may represent a reaction of neurons to lactate deficit, although it cannot reverse the energy deficiency in neurons.
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The combination of a deficit in astrocytic glucose uptake and neuronal lactate transporter density could lead to an energetic crisis and cognitive decline due to less lactate being supplied to neurons.
“The combination of a deficit in astrocytic glucose uptake and neuronal lactate transporter density (Zhang et al., 2018), could lead to an energetic crisis and cognitive decline due to less lactate being supplied to neurons.”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Zhang et al., 2018
Reduced glucose consumption could lead to a reduction in lactate production by astrocytes, as previously shown in different Alzheimer's disease models.
“This reduced glucose consumption, which partially reflects a reduction in glucose uptake by astrocytes, could therefore lead to a reduction in lactate production by astrocytes, as previously shown in different AD models (Le Douce et al., 2020; Lu et al., 2019; Zhang et al., 2018).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Zhang et al., 2018
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- Authors
- Zhang, M., Cheng, X., Dang, R., Zhang, W., Zhang, J., & Yao, Z.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Yao, Zhongxiang
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-11-01
- Volume
- 77
- Issue
- 12
- Pages
- 1163-1176
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2905362030
- Cited by
- 130
- References
- 5
- Citations by year
- 2026: 26 · 2025: 16 · 2024: 23 · 2023: 18 · 2022: 26 · 2021: 14 · 2020: 3 · 2019: 4
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31371147)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, lactate metabolism, lactate transporters, monocarboxylate transporters, lactate dehydrogenase, neuronal energy metabolism, brain energy metabolism, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mice, Transgenic, Neurons, Amyloid beta-Peptides, Lactic Acid, Mice, Presenilin-1
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