GABA Attenuates Amyloid Toxicity by Downregulating its Endocytosis and Improves Cognitive Impairment

GABA (gamma-aminobutyric acid) receptor modulators have been investigated as a potential treatment strategy in Alzheimer's disease (AD). In the present study, we found that GABA levels were different in wild type (WT) and A beta PP/PS1 mouse brains. GABA downregulated amyloid-beta (A beta) uptake in neurons through the receptor for advanced glycation end-products. Therefore, relative high levels of GABA decreased cytotoxicity induced by A beta in WT mice. GABA treatment decreased basal levels of cell death and the cell death induced by hydrogen peroxide in WT and A beta PP/PS1 neurons. Application of GABA during early life before 2 months of age can improve cognitive function significantly in A beta PP/PS1 mice. However, GABA treatment at 6 and 8 months of age cannot improve water maze performance. Activating or suppressing GABA(A) receptors by optogenetic methods also confirmed that GABA activation before 2 months of age increased water maze performance in A beta PP/PS1 mice. Our data suggest that GABA administration during early life can be a potential treatment for AD