Research done in a mouse model of AD.
The paywalled research paper is
https://www.cell.com/cell-metabolism/fu ... 20)30063-2
Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer’s Disease
Juliette Le Douce, Marianne Maugard, Julien Veran, Stéphane H.R. Oliet, Aude Panatier, Gilles Bonvento, et al.
Cell Metabolism, Volume 31, ISSUE 3, P503-517.e8, March 03, 2020
DOI: 10.1016/j.cmet.2020.02.004
Previous discussions regarding serine: https://www.apoe4.info/forums/search.ph ... mit=SearchHighlights
- Astrocytes have impaired glycolytic flux in a mouse model of Alzheimer’s disease
- Consequently, astrocytes produce less glycolysis-derived l-serine
- Low NMDAR occupancy by d-serine leads to impairment of synaptic plasticity and memory
Summary
- Dietary supplementation of l-serine restores synaptic plasticity and memory
Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer’s disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that the astrocytic l-serine biosynthesis pathway, which branches from glycolysis, is impaired in young AD mice and in AD patients. l-serine is the precursor of d-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity. Accordingly, AD mice display a lower occupancy of the NMDAR co-agonist site as well as synaptic and behavioral deficits. Similar deficits are observed following inactivation of the l-serine synthetic pathway in hippocampal astrocytes, supporting the key role of astrocytic l-serine. Supplementation with l-serine in the diet prevents both synaptic and behavioral deficits in AD mice. Our findings reveal that astrocytic glycolysis controls cognitive functions and suggest oral l-serine as a ready-to-use therapy for AD.
