Quantitative 1H and 31P MRS of PCA extracts of postmortem Alzheimer's disease brain

Klunk, William E.; Xu, Changhao; Panchalingram, K.; McClure, Richard J.; Pettegrew, Jay W.

doi:10.1016/0197-4580(96)00035-8

Cited by 78 publications

(73 citation statements)

References 35 publications

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“…The two PDEs, GPE and GPC, are effective at concentrations found in AD brain (Pettegrew et al. 1988a;Klunk et al, 1996). For example,~P MRS studies show that GPC levels in normal aged brain are ± 0.05 ftmol/g (or~-~l.2mM assuming 70% water content).…”

Section: Fig 5 Electron Micrographs Of A/li Aggregated In Pbs Buffermentioning

confidence: 99%

“…Neurofibrillary tangles arc intracellular deposits of an abnormally hyperphosphorylated cytoskeletal protein called tau (Goedert, 1993). Neuritic plaques and cerebrovascular amyloid are extracellular changes in levels of membrane phospholipid metaholites in postmortem AD brain (Pettegrew et al, l988a;Nitsch et al, 1992;Smith et al, 1993;Klunk et al, 1996). One of the most consistent findings is nearly twofold elevations in content of glycerophosphocholine (GPC), a phosphodiester (PDE) catabolic product of phosphatidylcholine metabolism (Nitsch et al, 1992;Klunk et al, 1996).…”

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confidence: 99%

“…Neuritic plaques and cerebrovascular amyloid are extracellular changes in levels of membrane phospholipid metaholites in postmortem AD brain (Pettegrew et al, l988a;Nitsch et al, 1992;Smith et al, 1993;Klunk et al, 1996). One of the most consistent findings is nearly twofold elevations in content of glycerophosphocholine (GPC), a phosphodiester (PDE) catabolic product of phosphatidylcholine metabolism (Nitsch et al, 1992;Klunk et al, 1996). In addition, postmortem magnetic resonance specti'oscopy (MRS) studies have demonstrated changes in certain phosphomonoesters (PM Es), which are both precursors to membrane phospholipid synthesis and membrane breakdown products (Klunk et al, 1996).…”

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confidence: 99%

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Aggregation of β‐Amyloid Peptide Is Promoted by Membrane Phospholipid Metabolites Elevated in Alzheimer's Disease Brain

Klunk

McClure

et al. 1997

Journal of Neurochemistry

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Abstract:Increased amounts of /3-amyloid (Aj3) peptide deposits are found in Alzheimer's disease brain. These amyloid deposits have been implicated in the pathophysiology of this common dementing illness. A/li peptides have been shown to be toxic to neurons in cell culture, and this toxicity is critically dependent on the aggregation of the peptide into cross-/li-pleated sheet fibrils. Also, in vivo and postmortem NMR studies have shown changes in certain brain membrane phospholipid metabolites in normal aging and more extensive alterations in patients with Alzheimer's disease. The finding that membrane phospholipids affect the aggregation of Ajli suggests that the abnormalities in membrane metabolism found in Alzheimer's disease could affect the deposition of A/li in vivo. Therefore, we examined the effect of membrane phospholipid metabolites that are altered in Alzheimer's disease brain on the aggregation of A/li(1 -40) using a light scattering method. Certain metabolites (glycerophosphocholine, glycerophosphoethanolamine, and a-glycerophosphate) augment the aggregation of A/li. Other membrane phospholipid metabolites (phosphocholine, phosphoethanolamine, and inositol-1-phosphate) have no effect. We conclude that increased membrane phospholipid metabolite concentrations may play a role in the deposition of A/li seen in normal aging and the even greater deposition of A/li observed in Alzheimer's disease.

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Section: Fig 5 Electron Micrographs Of A/li Aggregated In Pbs Buffermentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Aggregation of β‐Amyloid Peptide Is Promoted by Membrane Phospholipid Metabolites Elevated in Alzheimer's Disease Brain

Klunk

McClure

et al. 1997

Journal of Neurochemistry

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“…Succinate is a tricarboxylic acid cycle component present in brain at low concentrations, on the order of 0.5 mmol/kg wet weight [44]. In proton MRS, the resonance of succinate overlaps with those of glutamate and glutamine [43].…”

Section: Mrs-based Central Nervous System Biochemical Analysismentioning

confidence: 99%

The in-depth evaluation of suspected mitochondrial disease

Haas

Parikh

Falk

et al. 2008

Molecular Genetics and Metabolism

313

300

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Mitochondrial disease confirmation and establishment of a specific molecular diagnosis requires extensive clinical and laboratory evaluation. Dual genome origins of mitochondrial disease, multiorgan system manifestations, and an ever increasing spectrum of recognized phenotypes represent the main diagnostic challenges. To overcome these obstacles, compiling information from a variety of diagnostic laboratory modalities can often provide sufficient evidence to establish an etiology. These include blood and tissue histochemical and analyte measurements, neuroimaging, provocative testing, enzymatic assays of tissue samples and cultured cells, as well as DNA analysis. As interpretation of results from these multifaceted investigations can become quite complex, the Diagnostic Committee of the Mitochondrial Medicine Society developed this review to provide an overview of currently available and emerging methodologies for the diagnosis of primary mitochondrial disease, primarily focusing on disorders characterized by impairment of oxidative phosphorylation. The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease.

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“…The results replicate and extend previous SV MRS reports demonstrating the added value of measuring mI together with NAA. 12,16,18,21,24,55,64 The combined NAA/Cr and mI/Cr in parietal lobe GM by short TE 1H MRSI yielded a modest predictive value for distinguishing AD from normal subjects. In comparison, other 1H MRS studies reported classification rates ranging from 68% to 90% 10,24,47,65-68 ( Table 5).…”

Section: Value Of Using MI and Naa For Classificationmentioning

confidence: 99%

Effects of Alzheimer Disease on Fronto-parietal Brain N-acetyl Aspartate and Myo-Inositol Using Magnetic Resonance Spectroscopic Imaging

Zhu¹,

Schuff²,

Kornak³

et al. 2006

Alzheimer Disease &Amp; Associated Disorders

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Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/ Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD. KeywordsAlzheimer disease; short TE 1H magnetic resonance spectroscopic imaging; brain myo-Inositol Reprints: Xiaoping Zhu, MD, PhD, MR Unit, 114M, VA Medical Center/UCSF, 4150 Clement Street, San Francisco, CA 94121 (e-mail: zhupxia@itsa.ucsf.edu).. Sources of Support: Grant sponsor: NIH; Grant numbers: AG10897; AG12435; EB00207; EB00822; EB000766; Grant sponsor: VA Research: MIRECC, REAP. NIH Public Access Author ManuscriptAlzheimer Dis Assoc Disord. Author manuscript; available in PMC 2007 March 13. Published in final edited form as:Alzheimer Dis Assoc Disord. 2006 ; 20(2): 77-85. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlzheimer disease (AD) is characterized by accumulation of intraneuronal neurofibrillary tangles and extracellular amyloid plaques, as well as progressive loss of neurons that initially involve the hippocampal formation, temporoparietal cortex, and at later stages other cortical regions. 1-3 Such stereotypical regional spread of pathology may be delineated with imaging techniques, including structural magnetic resonance imaging (MRI), which showed brain tissue loss 4 and functional imaging by positron emission tomography (PET), which demonstrated cerebral glucose hypometabolism in AD. 5 However, neither structural MRI nor PET provides specific measures of neuronal or glial alterations.In vivo 1H magnetic resonance spectroscopy (MRS) has been used to measure levels of brain metabolites, such as N-acetyl aspartate (NAA) and myo-Inositol (mI) in AD. 6 Because NAA is found in relative...

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Quantitative 1H and 31P MRS of PCA extracts of postmortem Alzheimer's disease brain

Cited by 78 publications

References 35 publications

Aggregation of β‐Amyloid Peptide Is Promoted by Membrane Phospholipid Metabolites Elevated in Alzheimer's Disease Brain

Aggregation of β‐Amyloid Peptide Is Promoted by Membrane Phospholipid Metabolites Elevated in Alzheimer's Disease Brain

The in-depth evaluation of suspected mitochondrial disease

Effects of Alzheimer Disease on Fronto-parietal Brain N-acetyl Aspartate and Myo-Inositol Using Magnetic Resonance Spectroscopic Imaging

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