Abnormal cerebral metabolite concentrations in patients with probable alzheimer disease

Abstract

To establish whether recently described abnormalities of peak ratios are the result of changes in metabolite concentrations, quantitative 1H magnetic resonance spectroscopy was performed in 10 patients with Alzheimer disease (AD) and seven normal elderly. CSF volumes, metabolite T1 and T2 relaxation rates, ratios and concentrations of N-acetyl residues, creatine, choline residues, myo-inositol, glutamine plus glutamate (Glx), and glucose were obtained. Difference spectroscopy and quantitative assays showed a 50% increase in myo-inositol (6.4-9.8 mM; P < 0.005) and a decrease in N-acetyl in occipital gray matter. A reduction in beta, gamma-Glx and a significant increase in intracerebral [glucose], greater than attributable to CSF, were defined. Choline concentration increased with age, but was not elevated above normal in AD patients. These findings indicate the need for quantitative 1H MRS to substantiate metabolite ratios. The increased myo-inositol concentration in AD is demonstrated by these studies.

Hypermetabolic State in the 7-Month-Old Triple Transgenic Mouse Model of Alzheimer'S Disease and the Effect of Lipoic Acid: A 13C-NMR Study

“…Deuterium oxide (99.9%) and [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]acetate (99%) were obtained from Cambridge Isotope Laboratories (Andover, MA, USA). [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose (99%) was purchased from Sigma-Aldrich (St Louis, MO, USA) and all other chemicals were the purest grade available from Sigma-Aldrich.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose (99%) was purchased from Sigma-Aldrich (St Louis, MO, USA) and all other chemicals were the purest grade available from Sigma-Aldrich. Rodent tail vein catheter and restraining apparatus were obtained from Braintree Scientific (Braintree, MO, USA).…”

“…The current study was conducted to examine metabolic differences in the brain of 7-month-old 3xTg-AD and nonTg mice and assess the therapeutic effects of insulin mimetic, lipoic acid. [10][11][12] In addition to [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose infusion, the metabolic state was also probed with [1-13 C]glucose+ [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]acetate coinfusion to assess neuronal and astrocytic metabolism. Glucose is metabolized by both neurons and astrocytes; however, its major oxidative metabolism occurs in neurons, whereas, acetate is exclusively metabolized by astrocytes; thus, neuronal and astrocytic metabolism can be studied simultaneously by a co-infusion of 13 C-labeled glucose and acetate.…”

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

“…Alzheimer disease-A reasonable working hypothesis, subsequently confirmed in myriad studies, suggests that regional reductions in NAA concentration and NAA-creatine ratio are to be found in individual patients and in patient groups who test positive for clinical dementia. Patients with Alzheimer disease consistently show a 15-20% reduction in NAA/Cr (or NAA concentration) in posterior cingulate gyrus gray matter Moats et al, 1994;Shonk et al, 1995;Waldman et al, 2002). The gray matter in the region of the posterior cingulate gyrus has been found to be the most reliable for the diagnosis of this and other dementias, rather than hippocampus, the region selected for PET diagnosis, and postmortem histological examination of Alzheimer disease.…”

Simultaneous detection of resolved glutamate, glutamine, and γ-aminobutyric acid at 4T

“…Closely coupled to Glu, glutamine (Gln) is mostly located in glial cells as the end product of Glu catabolism and is a reservoir for Glu production in the neuron [1]. Due to a defective reuptake, excess Glu in the synaptic space will induce neurotoxicity, which has been linked to many degenerative diseases, including multiple sclerosis (MS) [2], amyotrophic lateral sclerosis (ALS) [3], Huntington's disease (HD) [4], and Alzheimer's disease (AD) [5], and to…”