Cortical amino acidergic pathways in Alzheimer's disease

Amino acidergic neurons in the cerebral cortex are the most abundant neuronal types. The inhibitory amino acid, GABA, is the neurotransmitter of many cortical interneurons, particularly those in layers III and IV of cerebral cortex. The excitatory amino acids, glutamate and aspartate, are the likely neurotransmitters of corticofugal, corticocortical association and hippocampal pyramidal neurons. In dementia of the Alzheimer type (DAT), there is only mild to moderate loss of GABAergic neurons and there is only a mild reduction in postsynaptic GABAA receptors. The unique bicuculline-insensitive baclofen-sensitive GABAB receptor is affected in DAT and is reduced by about 60-70% in outer layers of cerebral cortex and hippocampus. Presynaptic markers of glutamate neurons (glutamate levels and glutamate sodium-dependent binding) are reduced 25-80% in cortex and hippocampus of DAT brain. Likewise, glutamate postsynaptic receptors, particularly the NMDA-sensitive receptor, are markedly reduced in DAT cortex and hippocampus. These alterations suggest that glutamatergic pyramidal cells are especially vulnerable in DAT brain.