Molecular imaging of Alzheimer's disease

doi:10.1017/CBO9780511782091.026

25 - Molecular imaging of Alzheimer's disease

from Section IV - Cognitive Disorders

Published online by Cambridge University Press: 10 January 2011

Norbert Schuff

Edited by

Martha E. Shenton and

Bruce I. Turetsky

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Norbert Schuff: Affiliation:
Center for Imaging of Neurodegenerative Diseases at the Veterans Affairs Medical Center and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, CA, USA
Martha E. Shenton: Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky: Affiliation:
University of Pennsylvania

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Summary

Abstract

Neurochemical imaging offers an opportunity to study at a molecular level in-vivo the neuronal substrates that underpin Alzheimer's disease (AD) and related disorders, such as mild cognitive impairment (MCI). In particular, proton magnetic resonance spectroscopic imaging (1H MRSI) is unique among diagnostic imaging modalities because the method can measure several different brain metabolites simultaneously, including N-acetylaspartate (NAA), a neuronal integrity marker, and myo-inositol (MI), a potential glial marker. The goal of this chapter is to review key findings of 1H MRSI in AD, MCI and aging, and to discuss the potential value of this technology for diagnosis and prognosis of AD as well as for the assessment of therapeutic intervention. Other neurochemical imaging technologies such as direct mapping of neurotransmitter systems using emission tomography (PET) tracers and new trends, such as amyloid PET imaging are also briefly discussed.

Introduction

Alzheimer's disease (AD) is the most common cause of dementia and a growing health problem globally, affecting 20% of the population over 80 years of age (Ferri et al., 2005). Currently, the definite diagnosis of AD can only be made through autopsy to find the pathological hallmarks of the disease: microscopic amyloid plaques and neurofibrillary tangles. Macroscopically, AD is characterized by progressive loss of brain tissue that leads to a rapid decline in cognitive function.

Keywords

1H MRSI Alzheimer's disease amyloid PET imaging positron emission tomography neurotransmitter systems neurochemical imaging modalities mild cognitive impairment molecular imaging

Type: Chapter
Information: Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
, pp. 351 - 360

DOI: https://doi.org/10.1017/CBO9780511782091.026 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2010

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References

Ackl, N, Ising, M, Schreiber, Y A, Atiya, M, Sonntag, A and Auer, D P. 2005. Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease. Neurosci Lett 384, 23–8.Google Scholar

Adalsteinsson, E, Sullivan, E V, Kleinhans, N, Spielman, D M and Pfefferbaum, A. 2000. Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease. Lancet 355, 1696–7.Google Scholar

Birken, D L and Oldendorf, W H. 1989. N-acetyl-L-aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 13, 23–31.Google Scholar

Bitsch, A, Bruhn, H, Vougioukas, V, et al. 1999. Inflammatory CNS demyelination: Histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am J Neuroradiol 20, 1619–27.Google Scholar

Blakely, R D and Coyle, J T. 1988. The neurobiology of N-acetylaspartylglutamate. Int Rev Neurobiol 30, 39–100.Google Scholar

Braak, H and Braak, E. 1998. Evolution of neuronal changes in the course of Alzheimer's disease. J Neural Transm Suppl 53, 127–40.Google Scholar

Brand, A, Richter-Landsberg, C and Leibfritz, D. 1993. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15, 289–98.Google Scholar

Capizzano, A A, Schuff, N, Amend, D L, et al. 2000. Subcortical ischemic vascular dementia: Assessment with quantitative MR imaging and 1H MR spectroscopy. Am J Neuroradiol 21, 621–30.Google Scholar

Catani, M, Cherubini, A, Howard, R, et al. 2001. (1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging. Neuroreport 12, 2315–7.Google Scholar

Chantal, S, Braun, C M, Bouchard, R W, Labelle, M and Boulanger, Y. 2004. Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease. Brain Res 1003, 26–35.CrossRef Google Scholar

Chao, L L, Mueller, S G, Buckley, S T, et al. 2010. Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria. Neurobiol Aging 31, 368–77.Google Scholar

Chao, L L, Schuff, N, Kramer, J H, et al. 2005. Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients. Neurology 64, 282–9.Google Scholar

Dixon, R M, Bradley, K M, Budge, M M, Styles, P and Smith, A D. 2002. Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease. Brain 125, 2332–41.Google Scholar

Engelborghs, S and Deyn, P P. 1997. The neurochemistry of Alzheimer's disease. Acta Neurol Belg 97, 67–84.Google Scholar

Ernst, T, Chang, L, Melchor, R and Mehringer, C M. 1997. Frontotemporal dementia and early Alzheimer disease: Differentiation with frontal lobe H-1 MR spectroscopy. Radiology 203, 829–36.CrossRef Google Scholar

Fernandez, A, Garcia-Segura, J M, Ortiz, T, et al. 2005. Proton magnetic resonance spectroscopy and magnetoencephalographic estimation of delta dipole density: A combination of techniques that may contribute to the diagnosis of Alzheimer's disease. Dement Geriatr Cogn Disord 20, 169–77.CrossRef Google Scholar

Ferri, C P, Prince, M, Brayne, C, et al. 2005. Global prevalence of dementia: A Delphi consensus study. Lancet 366, 2112–7.Google Scholar

Forsberg, A, Engler, H, Almkvist, O, et al. 2008. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29, 1456–65.Google Scholar

Glanville, N T, Byers, D M, Cook, H W, Spence, M W and Palmer, F B. 1989. Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin. Biochim Biophys Acta 1004, 169–79.Google Scholar

Glodzik, L, King, K G, Gonen, O, Liu, S, Santi, S and Leon, M J. 2008. Memantine decreases hippocampal glutamate levels: A magnetic resonance spectroscopy study. Prog Neuropsychopharmacol Biol Psychiatry 32, 1005–12.Google Scholar

Guimaraes, A R, Schwartz, P, Prakash, M R, et al. 1995. Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain. Neuroscience 69, 1095–101.Google Scholar

Jessen, F, Block, W, Traber, F, et al. 2001. Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients. Neurology 57, 930–2.Google Scholar

Kadir, A, Almkvist, O, Wall, A, Langstrom, B and Nordberg, A. 2006. PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease. Psychopharmacology (Berl) 188, 509–20.Google Scholar

Kaiser, L G, Young, K, Meyerhoff, D J, Mueller, S G and Matson, G B. 2008. A detailed analysis of localized J-difference GABA editing: theoretical and experimental study at 4 T. NMR Biomed 21, 22–32.Google Scholar

Kantarci, K, Jack, C R, Xu, Y C, Campeau, N G, O'Brien, P C, Smith, G E, et al. 2000. Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study. Neurology 2000; 55: 210–7.Google Scholar

Kantarci, K, Knopman, D S, Dickson, D W, et al. 2008. Alzheimer disease: Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology 248, 210–20.Google Scholar

Kantarci, K, Smith, G E, Ivnik, R J, et al. 2002. 1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer's disease. J Int Neuropsychol Soc 8, 934–42.Google Scholar

Kantarci, K, Weigand, S D, Petersen, R C, et al. 2007. Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 28, 1330–9.Google Scholar

Kemppainen, N M, Aalto, S, Wilson, I A, et al. 2007. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68, 1603–06.Google Scholar

Kepe, V, Barrio, J R, Huang, S C, et al. 2006. Serotonin 1A receptors in the living brain of Alzheimer's disease patients. Proc Natl Acad Sci USA 103, 702–07.Google Scholar

Klein, J. 2000. Membrane breakdown in acute and chronic neurodegeneration: Focus on choline-containing phospholipids. J Neural Transm 107, 1027–63.Google Scholar

Klunk, W E, Panchalingam, K, Moossy, J, McClure, R J and Pettegrew, J W. 1992. N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer's disease brain: A preliminary proton nuclear magnetic resonance study. Neurology 42, 1578–85.Google Scholar

Koller, K J, Zaczek, R and Coyle, J T. 1984. N-acetyl-aspartyl-glutamate: Regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. J Neurochem 43, 1136–42.Google Scholar

Krishnan, K R, Charles, H C, Doraiswamy, P M, et al. 2003. Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. Am J Psychiatry 160, 2003–11.Google Scholar

Kuhl, D E, Koeppe, R A, Minoshima, S, et al. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 52, 691–9.Google Scholar

Lin, A P, Shic, F, Enriquez, C and Ross, B D. 2003. Reduced glutamate neurotransmission in patients with Alzheimer's disease – an in vivo (13)C magnetic resonance spectroscopy study. Magma 16, 29–42.Google Scholar

Metastasio, A, Rinaldi, P, Tarducci, R, et al. 2006. Conversion of MCI to dementia: Role of proton magnetic resonance spectroscopy. Neurobiol Aging 27, 926–32.Google Scholar

Meyerhoff, D J, MacKay, S, Constans, J M, et al. 1994. Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging. Ann Neurol 36, 40–7.Google Scholar

Mihara, M, Hattori, N, Abe, K, Sakoda, S and Sawada, T. 2006. Magnetic resonance spectroscopic study of Alzheimer's disease and frontotemporal dementia/Pick complex. Neuroreport 17, 413–6.Google Scholar

Moats, R A, Ernst, T, Shonk, T K and Ross, B D. 1994. Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med 32, 110–5.Google Scholar

Nordberg, A. 1993. Clinical studies in Alzheimer patients with positron emission tomography. Behav Brain Res 57, 215–24.Google Scholar

Nordberg, A, Hartvig, P, Lilja, A, et al. 1990. Decreased uptake and binding of 11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography. J Neural Transm Park Dis Dement Sect 2, 215–24.Google Scholar

Nordberg, A, Lundqvist, H, Hartvig, P, Lilja, A and Langstrom, B. 1995. Kinetic analysis of regional (S)(–)11C-nicotine binding in normal and Alzheimer brains – In vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9, 21–7.Google Scholar

Olson, B L, Holshouser, B A, Britt, W, et al. 2008. Longitudinal metabolic and cognitive changes in mild cognitive impairment patients. Alzheimer Dis Assoc Disord 22, 269–77.Google Scholar

Panza, F, D'Introno, A, Colacicco, A M, et al. 2005. Current epidemiology of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 13, 633–44.Google Scholar

Parnetti, L, Lowenthal, D T, Presciutti, O, et al. 1996. 1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease. J Am Geriatr Soc 44, 133–8.Google Scholar

Parnetti, L, Tarducci, R, Presciutti, O, et al. 1997. Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging. Mech Ageing Dev 97, 9–14.Google Scholar

Petersen, R C, Smith, G E, Waring, S C, Ivnik, R J, Tangalos, E G and Kokmen, E. 1999. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 56, 303–08.Google Scholar

Pfefferbaum, A, Adalsteinsson, E, Spielman, D, Sullivan, E V and Lim, K O. 1999. In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. Arch Gen Psychiatry 56, 185–92.Google Scholar

Price, J C, Klunk, W E, Lopresti, B J, et al. 2005. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 25, 1528–47.Google Scholar

Rose, S E, Zubicaray, G I, Wang, D, et al. 1999. A 1H MRS study of probable Alzheimer's disease and normal aging: Implications for longitudinal monitoring of dementia progression. Magn Reson Imaging 17, 291–9.Google Scholar

Ross, B, Lin, A, Harris, K, Bhattacharya, P and Schweinsburg, B. 2003. Clinical experience with 13C MRS in vivo. NMR Biomed 16, 358–69.Google Scholar

Schuff, N, Amend, D, Ezekiel, F, et al. 1997. Changes of hippocampal N-acetylaspartate and volume in Alzheimer's disease: A proton MR spectroscopic imaging and MRI study. Neurology 49, 1513–21.Google Scholar

Schuff, N, Capizzano, A A, Du, A T, et al. 2003. Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD. Neurology 61, 358–64.Google Scholar

Schuff, N, Capizzano, A A, Du, A T, et al. 2002. Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD. Neurology 58, 928–35.Google Scholar

Schuff, N, Ezekiel, F, Gamst, A C, et al. 2001. Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging. Magn Reson Med 45, 899–907.Google Scholar

Shinotoh, H, Fukushi, K, Nagatsuka, S, et al. 2003. The amygdala and Alzheimer's disease: Positron emission tomographic study of the cholinergic system. Ann N Y Acad Sci 985, 411–9.Google Scholar

Shonk, T K, Moats, R A, Gifford, P, et al. 1995. Probable Alzheimer disease: Diagnosis with proton MR spectroscopy. Radiology 195, 65–72.Google Scholar

Siger, M, Schuff, N, Zhu, X, Miller, B L and Weiner, M W. 2009. Regional myo-inositol concentration in mild cognitive impairment using 1H magnetic resonance spectroscopic imaging. Alzheimer Dis Assoc Disord 23, 57–62.Google Scholar

Simmons, M L, Frondoza, C G and Coyle, J T. 1991. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45, 37–45.Google Scholar

Tedeschi, G, Bertolino, A, Lundbom, N, et al. 1996. Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging. Neurology 47, 696–704.Google Scholar

Truchot, L, Costes, S N, Zimmer, L, et al. 2007. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment. Neurology 69, 1012–7.Google Scholar

Urenjak, J, Williams, S R, Gadian, D G and Noble, M. 1993. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13, 981–9.Google Scholar

Wyper, D J, Brown, D, Patterson, J, et al. 1993. Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease. Eur J Nucl Med 20, 379–86.Google Scholar

Zhu, X, Schuff, N, Kornak, J, et al. 2006. Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging. Alzheimer Dis Assoc Disord 20, 77–85.Google Scholar

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25 - Molecular imaging of Alzheimer's disease

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