Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology

Topic: Amyloid, tau and blood-test diagnosis

Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age-dependent Alzheimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. A number of amino acids [glutamate, aspartate, gamma-aminobutyrate (GABA), glycine, taurine, glutamine, serine, arginine] were investigated in post-mortem tissue samples from temporal, occipital cortex, thalamus, caudate nucleus, and cerebellum of adult patients with Down syndrome (DS) exhibiting Alzheimer-like neuropatholgy, Alzheimer's disease (AD) and from controls by use of high performance liquid chromatography (HPLC). In DS, no significant differences from control values could be observed in any of the brain regions. In AD, significant loss of GABA content was found in the temporal cortex (0.5+/-0.2 micromol/g vs. 1.3+/-0.8 micromol/g wet weight tissue, P<0.01), occipital cortex (0.8+/-0.2 micromol/g vs. 1.4+/-0.6 micromol/g, P<0.05) and cerebellum (1.1+/-0.3 micromol/g vs. 1.8+/-0.5 micromol/g, P<0.05). Glutamate and aspartate concentrations were significantly reduced in the caudate nucleus of AD subjects (glutamate: 6.1+/-3.4 micromol/g vs. 14.7+/-1.8 micromol/g; aspartate: 1.5+/-0.3 micromol/g vs. 3.3+/-0.4 micromol/g, P<0.05). The results of this study confirm previous findings in late stage AD and provide further information with respect to DS which may be relevant to understanding different pathogenesis of cognitive and non-cognitive (behavioral) features in DS and AD.

Key findings

• In DS, no significant differences from control values could be observed in any of the brain regions.
• In AD, significant loss of GABA content was found in the temporal cortex (0.5+/-0.2 micromol/g vs. 1.3+/-0.8 micromol/g wet weight tissue, P<0.01), occipital cortex (0.8+/-0.2 micromol/g vs. 1.4+/-0.6 micromol/g, P<0.05) and cerebellum (1.1+/-0.3 micromol/g vs. 1.8+/-0.5 micromol/g, P<0.05).
• Glutamate and aspartate concentrations were significantly reduced in the caudate nucleus of AD subjects (glutamate: 6.1+/-3.4 micromol/g vs. 14.7+/-1.8 micromol/g; aspartate: 1.5+/-0.3 micromol/g vs. 3.3+/-0.4 micromol/g, P<0.05).
• The results of this study confirm previous findings in late stage AD and provide further information with respect to DS which may be relevant to understanding different pathogenesis of cognitive and non-cognitive (behavioral) features in DS and AD.

Why it matters

In post-mortem brain tissue, this study found no significant differences in amino acid levels, including GABA, in Down syndrome compared with controls, while Alzheimer's disease showed significant losses of GABA and of glutamate and aspartate in some regions. It is a tissue comparison that identifies no treatment or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/s002100000346
• PubMed: 11218066
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{seidl2001-11218066,
  author  = {Seidl, R. and Cairns, N. and Singewald, N. and Kaehler, S. T. and Lubec, G.},
  title   = {{Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology}},
  journal = {Naunyn-Schmiedeberg's archives of pharmacology},
  year    = {2001},
  doi     = {10.1007/s002100000346},
  pmid    = {11218066},
  url     = {https://doi.org/10.1007/s002100000346}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neurology · 1991-04-01 · usefulness score 61/100 · Cognitive tests and assessment
• Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome Annals of Neurology · 1985-03-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Serotonin (5-HT) in brains of adult patients with Down syndrome Journal of neural transmission. Supplementum · 1999-01-01 · usefulness score 38/100 · Down syndrome and Alzheimer's

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• Dementia in Down's syndrome The Lancet. Neurology · 2016-04-11 · usefulness score 51/100 · Brain tissue and pathology
• Dissecting Alzheimer disease in Down syndrome using mouse models Frontiers in behavioral neuroscience · 2015-10-13 · usefulness score 40/100 · Down syndrome and Alzheimer's
• The brain in Down syndrome Journal of neural transmission. Supplementum · 2001-01-01 · usefulness score 34/100 · Down syndrome and Alzheimer's

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• Increased levels of tau-like protein in patients with Down syndrome Neuroscience letters · 1999-11-01 · usefulness score 29/100
• The importance of understanding individual differences in Down syndrome F1000Research · 2016-03-23 · usefulness score 40/100

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