Selective reduction of
            <i>N</i>
            -acetylaspartate in medial temporal and parietal lobes in AD

Schuff, Norbert; Capizzano, Arístides A.; Du, Antao; Amend, Diane; O’Neill, Joseph; Norman, David; Kramer, J. H.; Jagust, W.J.; Miller, Bruce L.; Wolkowitz, Owen M.; Yaffe, Kristine; Weiner, M W

doi:10.1212/wnl.58.6.928

Cited by 128 publications

(88 citation statements)

References 40 publications

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“…In the hippocampus, a relatively small structure in the magnetically inhomogeneous environs of the petrous temporal bone, localized short echo time MRS has measurement errors of 20% or more, sufficient to mask any biological differences in NAA associated with Alzheimer disease. On the other hand, use of the more robust MRS technique, long echo time chemical shift imaging confirms a loss of NAA from the hippocampus in Alzheimer disease which is directly proportional to the volume loss of that structure (Schuff et al, 2002). Schuff and colleagues have reported that NAA reductions and volume loss made independent contributions to the correct discrimination of Alzheimer disease patients from controls, with a better than 80% correct diagnosis using NAA declines alone, which improved to 90% when NAA loss and volume reductions were combined (Schuff et al, 2006).…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 96%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,230

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 96%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,230

1,126

View full text Add to dashboard Cite

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“…By utilizing MRS, reduced NAA and increased myo-inositol concentrations have been consistently found in the brain of AD patients compared to cognitively healthy elderly individuals and to be correlated to decline in cognitive performance (e.g. Chantal et al, 2002Chantal et al, , 2004Huang et al, 2001;Kantarci et al, 2004;Klunk et al, 1998;Jessen et al, 2000Jessen et al, , 2009Meyerhoff et al, 1994;Miller et al, 1993;Mohanakrishnan et al, 1997;Pfefferbaum et al, 1999a,b;Rose et al, 1999;Schuff et al, 2002;Watanabe et al, 2010). While NAA indicates loss of neuronal integrity, myo-inositol has been interpreted as a marker of gliosis (see discussion above).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

et al. 2012

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“…[17][18][19][20][21] The decrease of NAA or the NAA/creatine (Cr) ratio shows a regional variation in AD. [22][23][24] In patients with mild to moderate AD, NAA/Cr levels are lower than normal in the posterior cingulate gyrus, whereas they are normal in the medial occipital lobe, including in the visual cortex. 23 This regional pattern is in agreement with the distribution of the neurofibrillary pathology, and the associated neuron loss in people with mild to moderate AD, indicating that regional NAA/Cr levels are potential surrogates for disease progression.…”

mentioning

confidence: 99%

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

Kantarci

Jack

2004

Neurotherapeutics

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Summary: Recent advances in understanding the molecular biology of Alzheimer's disease (AD) offer the promise of useful therapeutic intervention in the foreseeable future. Hence, improved methods for early diagnosis and noninvasive surrogates of disease severity in AD have become more imperative. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy in AD remains to be tested in a positive disease-modifying drug trial. Recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques are also underway in MR imaging. As with indirect MR measures, these approaches of directly imaging the pathological substrate will need to undergo a validation process with longitudinal studies to prove their usefulness as surrogate markers in AD.

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Selective reduction of N -acetylaspartate in medial temporal and parietal lobes in AD

Abstract: Background-Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging.

Cited by 128 publications

References 40 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

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