GAD65, GAD67, and GABAT Immunostaining in Human Brain and Apparent GAD65 Loss in Alzheimer's Disease
Bibliographic record
Abstract
The GABAergic system is the main inhibitory neurotransmitter system in the vertebrate brain. Although it is well established that the GABAergic system is affected in neuropsychiatric disorders, in Alzheimer's disease (AD) it has been considered to be relatively spared. In this study we describe the immunohistochemical localization of the main enzymes of the GABAergic system; glutamate decarboxylase 65 (GAD65), GAD67, and GABA transferase (GABAT) in human brain. In neocortex, hippocampus, basal ganglia, and cerebellum, GAD65 and GAD67 immunoreactivity were found in neuropil granules, possibly axonal boutons or terminals, and in a subset of small to midsized neurons. GAD65 preferentially stained neuropil granules, while GAD67 preferentially stained neuronal cell bodies. GABAT intensely labeled many types of neurons and glia cells. While GAD65 and GAD67 stained the cytoplasm of cells homogeneously, GABAT labeling appeared irregular and granular. GAD65 immunoreactivity of neurons and neuropil was severely reduced in AD middle temporal gyrus, hippocampus, and putamen as determined by fluorescence and light microscopic immunohistochemistry. Western blotting revealed a similar reduction of GAD65, but not GAD67, protein levels in the middle temporal gyrus of AD. Our results suggest that the GABAergic system is more severely affected in AD than previously reported. This deficit may contribute to AD pathogenesis by loss of GABAergic inhibitory activity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".