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Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice
Open accessAbstract
Locus ceruleus (LC) degeneration and loss of cortical noradrenergic innervation occur early in Alzheimer’s disease (AD). Although this has been known for several decades, the contribution of LC degeneration to AD pathogenesis remains unclear. We induced LC degeneration with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) in amyloid precursor protein 23 (APP23) transgenic mice with a low amyloid load. Then 6 months later the LC projection areas showed a robust elevation of glial inflammation along with augmented amyloid plaque deposits. Moreover, neurodegeneration and neuronal loss significantly increased. Importantly, the paraventricular thalamus, a nonprojection area, remained unaffected. Radial arm maze and social partner recognition tests revealed increased memory deficits while high-resolution magnetic resonance imaging-guided micro-positron emission tomography demonstrated reduced cerebral glucose metabolism, disturbed neuronal integrity, and attenuated acetylcholinesterase activity. Nontransgenic mice with LC degeneration were devoid of these alterations. Our data demonstrate that the degeneration of LC affects morphology, metabolism, and function of amyloid plaque-containing higher brain regions in APP23 mice. We postulate that LC degeneration substantially contributes to AD development.
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“In contrast, lesioning of another projection pathway, that from the locus coeruleus, was reported to increase plaque pathology in terminal fields of the cerebral cortex [72].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [72]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140
Nucleus locus ceruleus: new evidence of anatomical and physiological specificity
Foote, S. L., Bloom, F. E., & Aston-Jones, G. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.3.844 · Cited by 1,901
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507
Self-citationWidespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease
Smith, M. A., Richey Harris, P. L., Sayre, L. M., Beckman, J. S., & Perry, G. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02653.1997 · Cited by 1,239
Zarow, C., Lyness, S. A., Mortimer, J. A., & Chui, H. C. (2003) · Archives of Neurology · doi:10.1001/archneur.60.3.337 · Cited by 1,003
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., et al. (1999) · Nature Neuroscience · doi:10.1038/6374 · Cited by 946
Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Herholz, K., Salmon, E., Perani, D., Baron, J.-C., Holthoff, V., Frölich, L., Schönknecht, P., Ito, K., Mielke, R., & Kalbe, E. (2002) · NeuroImage · doi:10.1006/nimg.2002.1208 · Cited by 832
Role for neuronal insulin resistance in neurodegenerative diseases
Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Küstermann, E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308724101 · Cited by 659
Self-citationEctopic Cell Cycle Proteins Predict the Sites of Neuronal Cell Death in Alzheimer’s Disease Brain
Busser, J., Geldmacher, D. S., & Herrup, K. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02801.1998 · Cited by 543
Disease‐specific patterns of locus coeruleus cell loss
German, D. C., Manaye, K. F., White, C. L., Woodward, D. J., McIntire, D. D., Smith, W. K., Kalaria, R. N., & Mann, D. M. A. (1992) · Annals of Neurology · doi:10.1002/ana.410320510 · Cited by 512
Neuron loss in APP transgenic mice
Calhoun, M. E., Wiederhold, K.-H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., & Jucker, M. (1998) · Nature · doi:10.1038/27351 · Cited by 502
Self-citationChanges in the Brain Catecholamines in Patients with Dementia of Alzheimer Type
Adolfsson, R., Gottfries, C. G., Roos, B. E., & Winblad, B. G. (1979) · The British Journal of Psychiatry · doi:10.1192/bjp.135.3.216 · Cited by 449
Noradrenergic mechanisms in neurodegenerative diseases: a theory
Marien, M. R., Colpaert, F. C., & Rosenquist, A. C. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.02.002 · Cited by 425
A Distinct Role for Norepinephrine in Memory Retrieval
Murchison, C., Zhang, X., Zhang, W., Ouyang, M., Lee, A., & THOMAS, S. A. (2004) · Cell · doi:10.1016/s0092-8674(04)00259-4 · Cited by 421
Sastre, M., Dewachter, I., Landreth, G. E., Willson, T. M., Klockgether, T., LEUVEN, F. V., & Heneka, M. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09796.2003 · Cited by 361
Self-citationMurray, C. A., & Lynch, M. A. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02974.1998 · Cited by 359
Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus
Hopkins, W. F., & Johnston, D. (1988) · Journal of Neurophysiology · doi:10.1152/jn.1988.59.2.667 · Cited by 310
Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.
Yoram Vodovotz, B., Lucia, M. S., Flanders, K. C., Chesler, L., Xie, Q. W., Smith, T. W., Weidner, J. R., Mumford, R. A., Webber, R., Nathan, C., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1425 · Cited by 292
Changes in the Monoamine Containing Neurones of the Human Cns in Senile Dementia
Mann, D. M. A., Lincoln, J., Yates, P. O., Stamp, J., & Toper, S. (1980) · The British Journal of Psychiatry · doi:10.1192/bjp.136.6.533 · Cited by 285
Blasko, I., Marx, F., Steiner, E., Hartmann, T., & Grubeck-Loebenstein, B. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.1.63 · Cited by 279
Iyo, M., Namba, H., Fukushi, K., Shinotoh, H., Nagatsuka, S., Suhara, T., Sudo, Y., Suzuki, K., & Irie, T. (1997) · The Lancet · doi:10.1016/s0140-6736(96)09124-6 · Cited by 259
Heneka, M. T., Galea, E., Gavriluyk, V., Dumitrescu‐Ozimek, L., Daeschner, J., O’Banion, M. K., Weinberg, G. L., Klockgether, T., & Feinstein, D. L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02434.2002 · Cited by 255
Self-citationThe radial arm maze as a tool in behavioral pharmacology
Olton, D. S. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90286-1 · Cited by 242
Fritschy, J., & Grzanna, R. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90364-3 · Cited by 235
Noradrenergic regulation of inflammatory gene expression in brain
Feinstein, D. L., Heneka, M. T., Gavrilyuk, V., Russo, C. D., Weinberg, G. L., & Galea, E. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00049-9 · Cited by 222
Self-citationBondolfi, L., Calhoun, M., Ermini, F., Kuhn, H. G., Wiederhold, K.-H., Walker, L., Staufenbiel, M., & Jucker, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00515.2002 · Cited by 213
Self-citationNoradrenergic changes, aggressive behavior, and cognition in patients with dementia
Matthews, K. L., Chen, C., Esiri, M. M., Keene, J., Minger, S. L., & Francis, P. T. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01235-5 · Cited by 211
Wang, Q., Rowan, M. J., & Anwyl, R. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0233-04.2004 · Cited by 197
Wong, T. P., Debeir, T., Duff, K., & Cuello, A. C. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02706.1999 · Cited by 196
Self-citationLüth, H.-J., Holzer, M., Gärtner, U., Staufenbiel, M., & Arendt, T. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02758-5 · Cited by 183
Self-citationNEURONAL DEGENERATION IN LOCUS CERULEUS AND CORTICAL CORRELATES OF ALZHEIMER DISEASE
Bondareff, W., Mountjoy, C. Q., Roth, M., Rossor, M. N., Iversen, L. L., Reynolds, G. P., & Hauser, D. L. (1987) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198701040-00005 · Cited by 166 · cited 3×
“The reduction of LC neurons correlates with amyloid- (A ) plaques, neurofibrillary tangles, and the severity of dementia (Bondareff et al., 1987).”
BackgroundCholinergic Changes in the APP23 Transgenic Mouse Model of Cerebral Amyloidosis
Boncristiano, S., Calhoun, M. E., Kelly, P. H., Pfeifer, M., Bondolfi, L., Stalder, M., Phinney, A. L., Abramowski, D., Sturchler-Pierrat, C., Enz, A., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03234.2002 · Cited by 160
Self-citationFrohman, E. M., Vayuvegula, B., Gupta, S., & van den Noort, S. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1292 · Cited by 142
Choline acetyltransferase immunoreactivity in the rat thalamus
Levey, A. I., Hallanger, A. E., & Wainer, B. H. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902570302 · Cited by 134
Stanton, P. K., & Sarvey, J. M. (1987) · Brain Research Bulletin · doi:10.1016/0361-9230(87)90039-6 · Cited by 121
The effect of norepinephrine on endotoxin-mediated macrophage activation
Hu, X., Goldmuntz, E. A., & Brosnan, C. F. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90084-k · Cited by 119
Debeir, T., Saragovi, H. U., & Cuello, A. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.4067 · Cited by 114
Self-citationJellinger, K. A. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)82406-9 · Cited by 104
Heiss, W., Graf, R., Fujita, T., Ohta, K., Bauer, B., Löttgen, J., & Wienhard, K. (1997) · Stroke · doi:10.1161/01.str.28.10.2045 · Cited by 79
Self-citationBluhm, M. D. L., Mateo, Y., Durkin, S., Parker, T. L., & Marsden, C. A. (2001) · Psychopharmacology · doi:10.1007/s002130100702 · Cited by 68
Förstl, H., Levy, R., Burns, A. S., Luthert, P. J., & Cairns, N. (1994) · Pharmacopsychiatry · doi:10.1055/s-2007-1014267 · Cited by 52
Willis, S. A., & Nisen, P. D. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.3.1399 · Cited by 52
Dudley, M. W., Howard, B. D., & Cho, A. K. (1990) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.30.040190.002131 · Cited by 48
Hanania, T., Hillman, G. R., & Johnson, K. M. (1999) · Synapse · doi:10.1002/(sici)1098-2396(19990301)31:3 · Cited by 46
Harro, J., Pähkla, R., Modiri, A., Harro, M., Kask, A., & Oreland, L. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050184 · Cited by 44
Spatial Learning and Noradrenaline Content in the Brain and Periphery of Young and Aged Rats
Sirviö, J., Lahtinen, H., Riekkinen, P. J., & Riekkinen, P. J. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1035 · Cited by 26
A Histochemical Examination of the Staining of Kainate-Induced Neuronal Degeneration by Anionic Dyes
Kiernan, J. A., Macpherson, C. M., Price, A. K., & Sun, T. (1998) · Biotechnic & Histochemistry · doi:10.3109/10520299809141118 · Cited by 23
Ohno, M., Yoshimatsu, A., Kobayashi, M., & Watanabe, S. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00353-x · Cited by 22
Bezin, L., Marcel, D., Rousset, C. I., Pujol, J. F., & Weissmann, D. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-12-07502.1994 · Cited by 19
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“…(Lassalle et al., 2008), 19: (Morgan et al., 2000), 20: (Sturchler-Pierrat et al., 1997), 21: (Van Dam et al., 2003), 22: (Huang et al., 2006), 23: (Heneka et al., 2006), 24: (Prut et al., 2007), 25: (Kelly et al., 2003), 26: (Lalonde et al., 2002), 27: (Dumont et al., 2004), 28: (Chishti et al.,…”
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Metadata
- Authors
- Heneka, M. T., Ramanathan, M., Jacobs, A. H., Dumitrescu-Ozimek, L., Bilkei-Gorzo, A., Debeir, T., Sastre, M., Galldiks, N., Zimmer, A., Hoehn, M., Heiss, W.-D., Klockgether, T., & Staufenbiel, M.
- Affiliations
- University of Bonn (DE)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-02-01
- Volume
- 26
- Issue
- 5
- Pages
- 1343-1354
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6675491
- OpenAlex
- W2118414216
- Cited by
- 305
- References
- 54
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 18 · 2023: 21 · 2022: 23 · 2021: 18 · 2020: 16 · 2019: 16 · 2018: 12 · 2017: 20 · 2016: 9 · 2015: 17 · 2014: 11 · 2013: 17 · 2012: 19
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB400)
- International Brain Research Organization
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease pathogenesis, glial inflammation, amyloid plaques, neurodegeneration, memory impairment, brain glucose metabolism, acetylcholinesterase activity, paraventricular thalamus, cholinergic hypothesis
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Brain, Cognition Disorders, Female, Locus Coeruleus, Mice, Transgenic, Nerve Degeneration, Norepinephrine, Amyloid beta-Protein Precursor, Microglia, Peroxynitrous Acid, Positron-Emission Tomography, Vesicular Acetylcholine Transport Proteins, Mice, Nitric Oxide Synthase Type II, Plaque, Amyloid
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