Glutamate Metabolizing Enzymes in Prefrontal Cortex of Alzheimer’s Disease Patients

Abstract

Amounts of glutamate metabolizing enzymes such as glutamate dehydrogenase (GDH), glutamine synthetase (GS), GS-like protein (GSLP), and phosphate-activated glutaminase (PAG) were compared in prefrontal cortex of control subjects and patients with Alzheimer disease (AD). The target proteins were quantified by ECL-Western immunoblotting in extracts from brain tissue prepared by two different techniques separating enzymes preferentially associated with cytoplasm (GDH I and II isoenzymes, GS, and partially GSLP) and membrane (GDH III, PAG, and partially GSLP) fractions. Amounts of all listed enzymes were found significantly increased in the patient group compared with controls. Some links between the measured values were observed in the control, but not in the AD patient group. The results may suggest for the pathological interruption of regulatory relations between distinct enzymes of glutamate metabolism in brain of AD patients.

Serum Glutamine Synthetase Has No Value as a Diagnostic Biomarker for Alzheimer’s Disease

“…Taken together, our study is the first to report unaltered serum GS concentrations in AD patients compared to age-matched control subjects and therefore suggests that there is no potential diagnostic value of serum GS for AD. This result is in contrast with some previous AD-related GS studies that found alterations of GS concentrations in serum [16], CSF [14,15] and brain tissue [4,5,17]. However, these studies did not share the same outcome as in serum and in CSF an increase of GS levels was found ( [16] and [15], respectively) whereas in brain tissue diverse outcomes were observed, with increases [17] but also with decreases [4,5] of reported GS levels.…”

“…Also, Tumani et al [15] did not include age-matched controls but a control group with a wide variety of ages. Moreover, Burbaeva et al [17], Le Prince et al [5], Smith et al [4], Takahashi et al [16] and Tumani et al [15] included only 11, 8, 16, 24 and 8 AD patients, respectively. Most studies also included less control subjects, with exception of the study of Takahashi et al [16].…”

“…Serum GS concentrations were higher in AD patients compared to controls although the level of statistical significance was not achieved [15]. Takahashi et al [16] measured elevated GS concentrations in serum of AD patients compared to non-AD dementias and Burbaeva et al [17] found increased levels of GS in the prefrontal cortex of AD patients compared to healthy controls. However, decreased GS levels have also been reported in brains of patients with AD [4,5,18], spinocerebellar ataxia type I [19] and hepatic encephalopathy [20], which might indicate a relationship between alterations in GS concentrations, oxidative stress and brain injury [4].…”

Creatine kinase isoform B distribution in the brain in schizophrenia

“…Определяли количество КФК В, исполь-зуя внутренний стандарт (образец мозга контрольной группы) [15] с помощью конъюгированных с пероксида-зой моноклональных мышиных антител в разведении 1:100 000. Антитела получены совместно с сотрудниками лаборатории клинической иммунологии ФГБНУ НЦПЗ.…”

“…2 приведен пример окрашивания при ECL-иммуноблоттинге иммунореактивной КФК В во фрак-ции водорастворимых белков мозжечка. Видно, что ин-тенсивность окрашивания полосы, соответствующей КФК В, в контроле значительно выше (дорожки 1-9), чем у больных ШЗ (10)(11)(12)(13)(14)(15)(16)(17). Как и активность КФК, ко-личество иммунореактивной КФК В во всех анализиро-ванных областях мозга было значительно снижено у больных ШЗ по сравнению с контролем (во всех случаях р<0,01) (рис.…”