Lactate Deficit in an Alzheimer Disease Mouse Model: The Relationship With Neuronal Damage

J Neuropathol Exp Neurol. 2018 Dec 1;77(12):1163-1176. doi: 10.1093/jnen/nly102.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Disease Models, Animal*
  • Lactic Acid / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Neurons / pathology
  • Presenilin-1 / genetics


  • Amyloid beta-Peptides
  • Presenilin-1
  • presenilin 1, mouse
  • Lactic Acid