PMID- 8245957
OWN - NLM
STAT- MEDLINE
DCOM- 19931223
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 61
IP  - 6
DP  - 1993 Dec
TI  - Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease.
PG  - 2007-14
AB  - We measured the activity of the alpha-ketoglutarate dehydrogenase complex 
      (alpha-KGDHC), a rate-limiting Krebs cycle enzyme, in postmortem brain samples 
      from 38 controls and 30 neuropathologically confirmed Alzheimer's disease (AD) 
      cases, in both the presence and absence of thiamine pyrophosphate (TPP), the 
      enzyme's cofactor. Statistically significant correlations between brain pH and 
      lactate levels and alpha-KGDHC activity in the controls were observed, suggesting 
      an influence of agonal status on the activity of alpha-KGDHC. As compared with 
      the controls, mean alpha-KGDHC activity, with added TPP, was significantly (p < 
      0.005) reduced in AD brain in frontal (-56%), temporal (-60%), and parietal 
      (-68%) cortices, with the reductions (-25 to -53%) in the occipital cortex, 
      hippocampus, amygdala, and caudate failing to reach statistical significance. In 
      the absence of exogenously administered TPP, mean alpha-KGDHC activity was 
      reduced to a slightly greater extent in all seven AD brain areas (-39 to -83%), 
      with the reductions now reaching statistical significance in the four cerebral 
      cortical areas and hippocampus. A statistically significant negative correlation 
      was observed between alpha-KGDHC activity and neurofibrillary tangle count in AD 
      parietal cortex, the brain area exhibiting the most marked reduction in enzyme 
      activity; this suggests that the enzyme activity reduction in AD brain may be 
      related to the disease process and severity. In each brain area examined, TPP 
      produced a greater stimulatory effect on alpha-KGDHC activity in the AD group 
      (23-280% mean stimulation) as compared with the controls (-4 to +50%); this TPP 
      effect could be explained by reduced endogenous TPP levels in AD brain.(ABSTRACT 
      TRUNCATED AT 250 WORDS)
FAU - Mastrogiacomo, F
AU  - Mastrogiacomo F
AD  - Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, 
      Toronto, Ontario, Canada.
FAU - Bergeron, C
AU  - Bergeron C
FAU - Kish, S J
AU  - Kish SJ
LA  - eng
GR  - NS26034/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Lactates)
RN  - EC 1.2.4.2 (Ketoglutarate Dehydrogenase Complex)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*enzymology
MH  - Autopsy
MH  - Brain/*enzymology/metabolism
MH  - Female
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Ketoglutarate Dehydrogenase Complex/*metabolism
MH  - Lactates/metabolism
MH  - Male
MH  - Organ Specificity
MH  - Reference Values
EDAT- 1993/12/01 00:00
MHDA- 1993/12/01 00:01
CRDT- 1993/12/01 00:00
PHST- 1993/12/01 00:00 [pubmed]
PHST- 1993/12/01 00:01 [medline]
PHST- 1993/12/01 00:00 [entrez]
AID - 10.1111/j.1471-4159.1993.tb07436.x [doi]
PST - ppublish
SO  - J Neurochem. 1993 Dec;61(6):2007-14. doi: 10.1111/j.1471-4159.1993.tb07436.x.