Enzyme Activities in Relation to pH and Lactate in Postmortem Brain in Alzheimer‐Type and Other Dementias
Abstract
Abstract: Phosphate‐activated glutaminase, glutamic acid decarboxylase, pyruvate dehydrogenase, succinic dehydrogenase, pH, and lactate were measured in frontal cortex and caudate nucleus of postmortem brains from cases of Alzheimer‐type dementia (ATD), Down's syndrome, Huntington's disease, and one case of Pick's disease, as well as from sudden death and agonal controls. Lactate levels were higher and pH, phosphate‐activated glutaminase, and glutamic acid decarboxylase levels were lower in the agonal controls than in the sudden death controls. Phosphate‐activated glutaminase and glutamic acid decarboxylase were correlated with tissue pH and lactate, and also were reduced by in vitro acidification, suggesting that the low activities of these enzymes in agonal controls were related to decreased pH consequent upon lactate accumulation. Compared with control tissues at the same pH, phosphate‐activated glutaminase and glutamic acid decarboxylase were unaltered in ATD and Down's frontal cortex and reduced in Huntington's caudate nucleus, and glutamic acid decarboxylase was reduced in Huntington's frontal cortex. These data suggest that GABAergic neurons are not affected in ATD and confirm the GABAergic defect in Huntington's disease. Pyruvate dehydrogenase and succinic dehydrogenase activities were the same in agonal controls and sudden death controls and were unaffected by acid pH and lactate in vitro, and pyruvate dehydrogenase was not correlated with pH or lactate. Reduced pyruvate dehydrogenase in frontal cortex of individual ATD, Down's, and Pick's cases. and in the caudate nucleus of Huntington's and Down's cases, was accompanied by gliosis/neuron loss. We conclude that decreased pyruvate dehydrogenase reflects neuronal loss.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Very few transcriptomic studies provide information on acute premortem variables or cause of death, which may potentially have a much larger effect on RNA quality and gene expression.
“Additionally, very few transcriptomic studies provide information on acute premortem variables or cause of death, which are particularly important as they may potentially have a much larger effect on RNA quality and gene expression71–76,78–80.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [78]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Neurotransmitter enzyme abnormalities in senile dementia
Perry, E. K., Gibson, P. H., Blessed, G., Perry, R. H., & Tomlinson, B. E. (1977) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(77)90073-9 · Cited by 724 · see citing works
Hohorst, H. J. (1965) · Elsevier eBooks · doi:10.1016/b978-0-12-395630-9.50058-x · Cited by 508 · see citing works
Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain
Sorbi, S., Bird, E. D., & Blass, J. P. (1983) · Annals of Neurology · doi:10.1002/ana.410130116 · Cited by 395 · see citing works
Transmitter deficits in Alzheimer's disease
Hardy, J., Adolfsson, R., Alafuzoff, I. I., Bucht, G., Marcusson, J. O., Nyberg, P., Perdahl, E., Wester, P. O., & Winblad, B. G. (1985) · Neurochemistry International · doi:10.1016/0197-0186(85)90050-6 · Cited by 329 · see citing works
Perry, E. K., Perry, R. H., Tomlinson, B. E., Blessed, G., & Gibson, P. H. (1980) · Neuroscience Letters · doi:10.1016/0304-3940(80)90220-7 · Cited by 236 · see citing works
Evidence of Glutamatergic Denervation and Possible Abnormal Metabolism in Alzheimer's Disease
PROCTER, A. W., Palmer, A. M., Francis, P. T., Lowe, S. L., Neary, D., Murphy, E., Doshi, R. N., & Bowen, D. M. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb02983.x · Cited by 197 · see citing works
Hardy, J. A., Wester, P., Winblad, B., Gezelius, C., Bring, G., & Eriksson, A. (1985) · Journal of Neural Transmission · doi:10.1007/bf01251916 · Cited by 185 · see citing works
An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain
Sheu, K. R., Kim, Y., Blass, J. P., & Weksler, M. E. (1985) · Annals of Neurology · doi:10.1002/ana.410170505 · Cited by 180 · see citing works
Lactate and pH in the Brain: Association and Dissociation in Different Pathophysiological States
Paschen, W., Djuričič, B., Mies, G., Schmidt‐Kastner, R., & Linn, F. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb13140.x · Cited by 177 · see citing works
Martin, J. B. (1984) · Neurology · doi:10.1212/wnl.34.8.1059 · Cited by 165 · see citing works
A post-mortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease
Reinikainen, K. J., Paljärvi, L., Huuskonen, M., Soininen, H. S., Laakso, M., & Riekkinen, P. J. (1988) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(88)90179-7 · Cited by 154 · see citing works
Butterworth, J. B., Yates, C. M., & Reynolds, G. P. (1985) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(85)90112-1 · Cited by 141 · see citing works
Self-citationTopographical distribution of neurochemical changes in Alzheimer's disease
PROCTER, A. W., Lowe, S. L., Palmer, A. M., Francis, P. T., Esiri, M. M., Stratmann, G. C., Najlerahim, A., Patel, A. J., Hunt, A., & Bowen, D. M. (1988) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(88)90118-9 · Cited by 137 · see citing works
GAMMA-AMINOBUTYRIC ACID CONCENTRATION IN BRAIN TISSUE AT TWO STAGES OF ALZHEIMER'S DISEASE
Lowe, S. L., Francis, P. T., PROCTER, A. W., Palmer, A. M., DAVISON, A. N., & Bowen, D. M. (1988) · Brain · doi:10.1093/brain/111.4.785 · Cited by 132 · see citing works
The influence of agonal status on some neurochemical activities of postmortem human brain tissue
Perry, E. K., Perry, R. H., & Tomlinson, B. E. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90334-2 · Cited by 125 · see citing works
Donoghue, J. P., Wenthold, R. J., & Altschuler, R. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-10-02597.1985 · Cited by 115 · see citing works
BIOCHEMICAL STUDIES OF NERVE CELLS AND ENERGY METABOLISM IN ALZHEIMER'S DISEASE
Bowen, D. M., & Davison, A. N. (1986) · British Medical Bulletin · doi:10.1093/oxfordjournals.bmb.a072102 · Cited by 105 · see citing works
Bagley, P. R., Tucker, S. P., Nolan, C. C., LINDSAY, J. G., Davies, A., Baldwin, S. A., Cremer, J. E., & Cunningham, V. J. (1989) · Brain Research · doi:10.1016/0006-8993(89)90769-5 · Cited by 60 · see citing works
Loss of glutaminase-positive cortical neurons in Alzheimer's disease
Akiyama, H., McGeer, P. L., Itagaki, S., McGeer, E. G., & Kaneko, T. (1989) · Neurochemical Research · doi:10.1007/bf01000038 · Cited by 42 · see citing works
Bowen, D. M., Goodhardt, M., Strong, A. J., Smith, C. B., White, P., Branston, N. M., Symon, L., & DAVISON, A. N. (1976) · Brain Research · doi:10.1016/0006-8993(76)90757-5 · Cited by 36 · see citing works
Phosphate‐Activated Glutaminase in Relation to Huntington's Disease and Agonal State
Butterworth, J., Yates, C. M., & Simpson, J. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb04761.x · Cited by 36 · see citing works
Self-citationSvenneby, G., Roberg, B., Hogstad, S., et al. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb00764.x · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009 · see citing works
Butterfield, D. A., Reed, T., Newman, S. F., & Sultana, R. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.05.037 · Cited by 564 · see citing works
Brain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · see citing works
Zhang, Z., Song, M., Liu, X., Kang, S. S., Kwon, I.-S., Duong, D. M., Seyfried, N. T., Hu, W. T., Liu, Z., Wang, J.-Z., et al. (2014) · Nature Medicine · doi:10.1038/nm.3700 · Cited by 494 · see citing works
Beach, T. G., Adler, C. H., Sue, L. I., Serrano, G., Shill, H. A., Walker, D. G., Lue, L., Roher, A. E., Dugger, B. N., Maarouf, C., et al. (2015) · Neuropathology · doi:10.1111/neup.12189 · Cited by 460 · see citing works
Marsh, S. E., Walker, A. J., Kamath, T., Dissing-Olesen, L., Hammond, T. R., de Soysa, T. Y., Young, A. M. H., Murphy, S., Abdulraouf, A., Nadaf, N., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01022-8 · Cited by 432 · see citing works
Abnormalities of mitochondrial enzymes in Alzheimer disease
Gibson, G. E., Sheu, K.-F. R., & Blass, J. P. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050099 · Cited by 345 · see citing works
Metal complexing agents as therapies for Alzheimer’s disease
Bush, A. I. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00120-3 · Cited by 310 · see citing works
Li, J. Z., Vawter, M. P., Walsh, D. M., Tomita, H., Evans, S. J., Choudary, P. V., Lopez, J. F., Avelar, A., Shokoohi, V., Chung, T., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh065 · Cited by 261 · see citing works
New Insights on How Metals Disrupt Amyloid β-Aggregation and Their Effects on Amyloid-β Cytotoxicity
Yoshiike, Y., Tanemura, K., Murayama, O., Akagi, T., Murayama, M., Sato, S., Sun, X., Tanaka, N., & Takashima, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010706200 · Cited by 244 · see citing works
Lanctôt, K. L., Herrmann, N., Mazzotta, P., Khan, L. R., & Ingber, N. (2004) · The Canadian Journal of Psychiatry · doi:10.1177/070674370404900705 · Cited by 191 · see citing works
Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study
Durrenberger, P. F., Fernando, S., Kashefi, S. N., Ferrer, I., Hauw, J.-J., Seilhean, D., Smith, C., Walker, R., Al-Sarraj, S., Troakes, C., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c7e32f · Cited by 161 · see citing works
Storr, T., Merkel, M., Song-Zhao, G. X., Scott, L. E., Green, D. E., Bowen, M. L., Thompson, K. H., Patrick, B. O., Schugar, H. J., & Orvig, C. (2007) · Journal of the American Chemical Society · doi:10.1021/ja068965r · Cited by 156 · see citing works
Mitochondria in Alzheimer's disease
Swerdlow, R. H., & Kish, S. J. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)53013-0 · Cited by 126 · see citing works
Monoranu, C. M., Apfelbacher, M., Grünblatt, E., Puppe, B., Alafuzoff, I., Ferrer, I., Al‐Saraj, S., Keyvani, K., Schmitt, A., Falkai, P., et al. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.01003a.x · Cited by 121 · see citing works
Tissue preparation and banking
Webster, M. J. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(06)58001-x · Cited by 67 · see citing works
C/EBPβ/AEP Signaling Drives Alzheimer’s Disease Pathogenesis
Xiong, J., Zhang, Z., & Ye, K. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01025-w · Cited by 37 · see citing works
Liu, Y., Kochi, A., Pithadia, A. S., Lee, S., Nam, Y., Beck, M. W., He, X., Lee, D., & Lim, M. H. (2013) · Inorganic Chemistry · doi:10.1021/ic400851w · Cited by 30 · see citing works
- Authors
- Yates, C. M., Butterworth, J., Tennant, M. C., & Gordon, A.
- Affiliations
- University of Edinburgh (GB)
- Royal Hospital for Sick Children (GB)
- Western General Hospital (GB)
- Corresponding author
- Yates, Celia M.
- ORCID
- Gordon, Alexander
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1990-11
- Volume
- 55
- Issue
- 5
- Pages
- 1624-1630
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1982682496
- Cited by
- 263
- References
- 23
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 7
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer-type dementia, Down syndrome, Huntington's disease, Pick's disease, postmortem brain, phosphate-activated glutaminase, glutamic acid decarboxylase, pyruvate dehydrogenase, succinate dehydrogenase, lactate, tissue pH, frontal cortex, caudate nucleus, GABAergic neurons, neuronal loss, gliosis, acidification
- MeSH terms
- Alzheimer Disease, Dementia, Humans, Hydrogen-Ion Concentration, Lactates, Neurons, Postmortem Changes, Reference Values, Lactic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
