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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

Open Access 01-03-2008

Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer’s disease

Authors: A. Winkeler, Y. Waerzeggers, A. Klose, P. Monfared, A. V. Thomas, M. Schubert, M. T. Heneka, A. H. Jacobs

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Special Issue 1/2008

Abstract

Introduction

Molecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level.

Imaging of AD characteristic changes by μPET

The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research.

Summary

In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimers’ disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases.

Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 1986;83:4913–7.PubMedCrossRef

Selkoe DJ. Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 2004;6:1054–61.PubMedCrossRef

Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991;349:704–6.PubMedCrossRef

Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, et al. Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 1995;269:973–7.PubMedCrossRef

Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 1995;376:775–8.PubMedCrossRef

Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 1995;375:754–60.PubMedCrossRef

Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, et al. A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet 1992;1:345–7.PubMedCrossRef

Higgins GA, Jacobsen H. Transgenic mouse models of Alzheimer’s disease: phenotype and application. Behav Pharmacol 2003;14:419–38.PubMed

Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996;274:99–102.PubMedCrossRef

10.

Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Nat Acad Sci U S A 1997;94:13287–92.CrossRef

11.

Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 1995;373:523–7.PubMedCrossRef

12.

Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, et al. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 1996;383:710–3.PubMedCrossRef

13.

Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 1998;4:97–100.PubMedCrossRef

14.

Heiss WD, Graf R, Wienhard K. Relevance of experimental ischemia in cats for stroke management: a comparative reevaluation. Cerebrovasc Dis (Basel, Switzerland) 2001;11:73–81.CrossRef

15.

Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G. Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain 2001;124:20–9.PubMedCrossRef

16.

Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frolich L, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 2002;17:302–16.PubMedCrossRef

17.

Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA 2001;286:2120–7.PubMedCrossRef

18.

Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 1997;42:85–94.PubMedCrossRef

19.

Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, et al. Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 1996;334:752–8.PubMedCrossRef

20.

Iyo M, Namba H, Fukushi K, Shinotoh H, Nagatsuka S, Suhara T, et al. Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer’s disease. Lancet 1997;349:1805–9.PubMedCrossRef

21.

Herholz K, Bauer B, Wienhard K, Kracht L, Mielke R, Lenz MO, et al. In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism. J Neural Transm 2000;107:1457–68.PubMedCrossRef

22.

Namba H, Fukushi K, Nagatsuka S, Iyo M, Shinotoh H, Tanada S, et al. Positron emission tomography: quantitative measurement of brain acetylcholinesterase activity using radiolabeled substrates. Methods 2002;27:242–50.PubMedCrossRef

23.

Shinotoh H, Namba H, Fukushi K, Nagatsuka S, Tanaka N, Aotsuka A, et al. Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer’s disease: a positron emission tomography study. Ann Neurol 2000;48:194–200.PubMedCrossRef

24.

Rinne JO, Kaasinen V, Jarvenpaa T, Nagren K, Roivainen A, Yu M, et al. Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2003;74:113–5.PubMedCrossRef

25.

Thomas A, Klein JC, Galldiks N, Hilker R, Grond M, Jacobs AH. Multitracer PET imaging in Heidenhain variant of Creutzfeldt–Jakob disease. J Neurol 2005.

26.

Bacskai BJ, Kajdasz ST, Christie RH, Carter C, Games D, Seubert P, et al. Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat Med 2001;7:369–72.PubMedCrossRef

27.

Klunk WE, Bacskai BJ, Mathis CA, Kajdasz ST, McLellan ME, Frosch MP, et al. Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative. J Neuropathol Exp Neurology 2002;61:797–805.

28.

Mathis CA, Bacskai BJ, Kajdasz ST, McLellan ME, Frosch MP, Hyman BT, et al. A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 2002;12:295–8.PubMedCrossRef

29.

Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004;55:306–19.PubMedCrossRef

30.

Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, et al. Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci 2001;21:RC189.PubMed

31.

Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 2002;10:24–35.PubMed

32.

Toyama H, Ye D, Ichise M, Liow JS, Cai L, Jacobowitz D, et al. PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2005;32:593–600.PubMedCrossRef

33.

Klunk WE, Lopresti BJ, Debnath ML, Holt DP, Wang Y, Huang G-F, et al. P2-031 Amyloid deposits in transgenic PS1/APP mice do not bind the amyloid pet tracer, PIB, in the same manner as human brain amyloid. Neurobiol Aging 2004;25:S232–S33.CrossRef

34.

Klunk WE, Lopresti BJ, Ikonomovic MD, Lefterov IM, Koldamova RP, Abrahamson EE, et al. Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 2005;25:10598–606.PubMedCrossRef

35.

McGowan E, Sanders S, Iwatsubo T, Takeuchi A, Saido T, Zehr C, et al. Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol Dis 1999;6:231–44.PubMedCrossRef

36.

Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 2004;101:3100–5.PubMedCrossRef

37.

Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, et al. Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J Neurosci 2006;26:1343–54.PubMedCrossRef

Title: Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer’s disease
Authors: A. Winkeler
Y. Waerzeggers
A. Klose
P. Monfared
A. V. Thomas
M. Schubert
M. T. Heneka
A. H. Jacobs
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue Special Issue 1/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0710-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer’s disease

Abstract

Introduction

Imaging of AD characteristic changes by μPET

Summary

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Imaging of AD characteristic changes by μPET

Summary

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