Olfactory Dysfunction Correlates with Amyloid-β Burden in an Alzheimer's Disease Mouse Model
Open accessAbstract
Alzheimer's disease often results in impaired olfactory perceptual acuity—a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-β (Aβ) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-β precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically—some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar Aβ deposition within the olfactory bulb—earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of Aβ deposition. Therefore, nonfibrillar, versus fibrillar, Aβ-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Aβ deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Aβ.
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Deficiencies in olfactory cross-habituation indicate incorrect decoding in the piriform cortex from sensory input from the olfactory bulb due to Aβ.
“Deficiencies in olfactory cross-habituation indicate incorrect decoding in the piriform cortex from sensory input from the olfactory bulb due to Aβ32.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [32]
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Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Rankin, C. H., Abrams, T., Barry, R. J., Bhatnagar, S., Clayton, D. F., Colombo, J., Coppola, G., Geyer, M. A., Glanzman, D. L., Marsland, S., et al. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.09.012 · Cited by 1,665 · see citing works
Self-citationAPP 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 · see citing works
An english translation of alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”
Stelzmann, R. A., Norman Schnitzlein, H., & Reed Murtagh, F. (1995) · Clinical Anatomy · doi:10.1002/ca.980080612 · Cited by 1,455 · see citing works
Two functional components of the hippocampal memory system
Eichenbaum, H., Otto, T., & Cohen, N. J. (1994) · Behavioral and Brain Sciences · doi:10.1017/s0140525x00035391 · Cited by 1,094 · see citing works
Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 3× · see citing works
“Tg2576 mice express an APP mutation (KM670/671NL), possess elevated soluble A in the neocortex at 7 months of age (Kawarabayashi et al., 2001), and start displaying fibrillar A deposits in the hippocampus and neocortex 10 months of age (Hsiao et al.”
BackgroundResultSoluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior
Selkoe, D. J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.016 · Cited by 1,038 · see citing works
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818 · see citing works
Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus
Puzzo, D., Privitera, L., Leznik, E., Fà, M., Staniszewski, A., Palmeri, A., & Arancio, O. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2692-08.2008 · Cited by 740 · see citing works
Haberly, L. B. (2001) · Chemical Senses · doi:10.1093/chemse/26.5.551 · Cited by 673 · see citing works
Mesholam, R. I., Moberg, P. J., Mahr, R. N., & Doty, R. L. (1998) · Archives of Neurology · doi:10.1001/archneur.55.1.84 · Cited by 643 · see citing works
EARLY EVENTS IN OLFACTORY PROCESSING
Wilson, R. I., & Mainen, Z. F. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112950 · Cited by 395 · see citing works
Sniffing controls an adaptive filter of sensory input to the olfactory bulb
Verhagen, J. V., Wesson, D. W., Netoff, T. I., White, J. A., & Wachowiak, M. (2007) · Nature Neuroscience · doi:10.1038/nn1892 · Cited by 381 · see citing works
Self-citationCoding and synaptic processing of sensory information in the glomerular layer of the olfactory bulb
Wachowiak, M., & Shipley, M. T. (2006) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2006.04.007 · Cited by 301 · see citing works
Mechanisms of olfactory dysfunction in aging and neurodegenerative disorders
Kovács, T. (2004) · Ageing Research Reviews · doi:10.1016/j.arr.2003.10.003 · Cited by 248 · see citing works
Learning to smell: olfactory perception from neurobiology to behavior
(2006) · Choice Reviews Online · doi:10.5860/choice.44-2108 · Cited by 235 · see citing works
Habituation of Odor Responses in the Rat Anterior Piriform Cortex
Wilson, D. A. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.3.1425 · Cited by 233 · see citing works
Self-citationOlfactory Bulb Gamma Oscillations Are Enhanced with Task Demands
Beshel, J., Kopell, N., & Kay, L. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1199-07.2007 · Cited by 222 · see citing works
Gao, Y., & Pimplikar, S. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261463298 · Cited by 218 · see citing works
Rapid Encoding and Perception of Novel Odors in the Rat
Wesson, D. W., Carey, R. M., Verhagen, J. V., & Wachowiak, M. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060082 · Cited by 216 · see citing works
Self-citationDissociable Codes of Odor Quality and Odorant Structure in Human Piriform Cortex
Gottfried, J. A., Winston, J. S., & Dolan, R. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.007 · Cited by 214 · see citing works
Olfactory perceptual stability and discrimination
Barnes, D. C., Hofacer, R. D., Zaman, A. R., Rennaker, R. L., & Wilson, D. A. (2008) · Nature Neuroscience · doi:10.1038/nn.2217 · Cited by 209 · see citing works
Self-citationLiu, Y., Yoo, M.-J., Savonenko, A., Stirling, W., Price, D. L., Borchelt, D. R., Mamounas, L., Lyons, W. E., Blue, M. E., & Lee, M. K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4218-08.2008 · Cited by 206 · see citing works
Hippocampal denervation causes rapid forgetting of olfactory information in rats.
Staubli, U. V., Ivy, G. O., & LYNCH, G. S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5885 · Cited by 195 · see citing works
Cystatin C inhibits amyloid-β deposition in Alzheimer's disease mouse models
Mi, W., Pawlik, M., Sastre, M., Jung, S. S., Radvinsky, D. S., Klein, A. M., Sommer, J., Schmidt, S. D., Nixon, R. A., Mathews, P. M., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.29 · Cited by 189 · see citing works
Self-citationSpatial coding of odorant features in the glomerular layer of the rat olfactory bulb
Johnson, B. A., Woo, C. C., & Leon, M. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980420)393:4 · Cited by 187 · see citing works
Separate encoding of identity and similarity of complex familiar odors in piriform cortex
Kadohisa, M., & Wilson, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604313103 · Cited by 171 · see citing works
Self-citationLoss of olfactory function in dementing disease.
Murphy, C. (1999) · Physiology and Behavior · doi:10.1016/s0031-9384(98)00262-5 · Cited by 163 · see citing works
Olfactory dysfunction as a predictor of neurodegenerative disease
Albers, M. W., Tabert, M. H., & Devanand, D. P. (2006) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-996-0018-7 · Cited by 147 · see citing works
Response properties of isolated mouse olfactory receptor cells
Reisert, J., & Matthews, H. R. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0113m.x · Cited by 140 · see citing works
Aβ Oligomers Induce Neuronal Cell Cycle Events in Alzheimer's Disease
Varvel, N. H., Bhaskar, K., Patil, A. R., Pimplikar, S. W., Herrup, K., & Lamb, B. T. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2441-08.2008 · Cited by 138 · see citing works
Fletcher, M. L., & Wilson, D. A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-02-j0005.2002 · Cited by 138 · see citing works
Self-citationAdrenergic modulation of olfactory bulb circuitry affects odor discriminationPreprint
Doucette, W. T., Milder, J., & Restrepo, D. (2007) · Learning & Memory · doi:10.1101/lm.606407 · Cited by 137 · see citing works
Sex Difference in Attraction Thresholds for Volatile Odors from Male and Estrous Female Mouse Urine
Baum, M. J., & Keverne, E. B. (2002) · Hormones and Behavior · doi:10.1006/hbeh.2001.1749 · Cited by 127 · see citing works
Olfactory Cortical Adaptation Facilitates Detection of Odors Against Background
Kadohisa, M., & Wilson, D. A. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00812.2005 · Cited by 126 · see citing works
Self-citationIllig, K. R. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20595 · Cited by 125 · see citing works
Spontaneous versus Reinforced Olfactory Discriminations
Linster, C., Johnson, B. A., Morse, A., Yue, E. L., & Leon, M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-16-06842.2002 · Cited by 123 · see citing works
Neurobiology of a Simple Memory
Wilson, D. A., & Linster, C. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90479.2008 · Cited by 112 · see citing works
Self-citationCoordinate Synaptic Mechanisms Contributing to Olfactory Cortical Adaptation
Best, A. R., & Wilson, D. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4220-03.2004 · Cited by 111 · see citing works
Self-citationCortical contributions to olfaction: Plasticity and perception
Wilson, D. A., Kadohisa, M., & Fletcher, M. L. (2006) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2006.04.008 · Cited by 87 · see citing works
Self-citationSchwob, J. E., & Price, J. L. (1978) · Brain Research · doi:10.1016/0006-8993(78)90891-0 · Cited by 84 · see citing works
Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice
Guérin, D., Sacquet, J., Mandairon, N., Jourdan, F., & Didier, A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.05.020 · Cited by 82 · see citing works
Linster, C., Menon, A. V., Singh, C. Y., & Wilson, D. A. (2009) · Learning & Memory · doi:10.1101/lm.1403509 · Cited by 66 · see citing works
Self-citationA method for studying responses and habituation to odors in rats
Sundberg, H., Döving, K. B., Novikov, S., et al. (1982) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(82)91501-1 · Cited by 62 · see citing works
Progressive impairment in olfactory working memory in a mouse model of Mild Cognitive Impairment
Young, J. W., Sharkey, J., & Finlayson, K. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.018 · Cited by 59 · see citing works
Alterations in β-amyloid production and deposition in brain regions of two transgenic models
Lehman, E. J. H., Kulnane, L. S., & Lamb, B. T. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00153-7 · Cited by 55 · see citing works
Yadon, C. A., & Wilson, D. A. (2005) · Learning & Memory · doi:10.1101/lm.41405 · Cited by 33 · see citing works
Self-citationZhuo, J., Prakasam, A., Murray, M. E., Zhang, H.-Y., Baxter, M. G., Sambamurti, K., & Nicolle, M. M. (2008) · Current Alzheimer Research · doi:10.2174/156720508785132280 · Cited by 33 · see citing works
Montgomery, K. S., Simmons, R. K., Edwards, G. A., Nicolle, M. M., Gluck, M. A., Myers, C. E., & Bizon, J. L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.003 · Cited by 30 · see citing works
Dijck, A. V., Vloeberghs, E., Dam, D. V., Staufenbiel, M., & Deyn, P. P. D. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.014 · Cited by 16 · see citing works
Wachowiak, M. (2009) · Frontiers in neuroscience · doi:10.1201/9781420071993-c12 · Cited by 10 · see citing works
Active Sensing in Olfaction -- The Neurobiology of Olfaction
Menini, A. (2010) · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Rankin CH Abrams T Barry RJ Bhatnagar S Clayton DF Colombo J Coppola G Geyer MA Glanzman DL Marsland S McSweeney FK Wilson DA Wu C-F Thompson RF 2009 Habituation revisited: An updated and revised description of the behavioral characteristics of habituation Neurobiology of Learning and Memory 92 135 138 18854219 PMC2754195
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Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050 · see citing works
Self-citationAt the interface of sensory and motor dysfunctions and Alzheimer’s disease.
Albers, M. W., Gilmore, G. C., Kaye, J., Murphy, C., Wingfield, A., Bennett, D. A., Boxer, A. L., Buchman, A. S., Cruickshanks, K. J., Devanand, D. P., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.514 · Cited by 589 · see citing works
Self-citationYang, D.-S., Stavrides, P., Mohan, P. S., Kaushik, S., Kumar, A., Ohno, M., Schmidt, S. D., Wesson, D., Bandyopadhyay, U., Jiang, Y., et al. (2011) · Brain · doi:10.1093/brain/awq341 · Cited by 429 · see citing works
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Laske, C., Sohrabi, H. R., Frost, S. M., López-de-Ipiña, K., Garrard, P., Buscema, M., Dauwels, J., Soekadar, S. R., Mueller, S., Linnemann, C., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.06.004 · Cited by 316 · see citing works
Ma, T., Hoeffer, C. A., Capetillo-Zarate, E., Yu, F., Wong, H., Lin, M. T., Tampellini, D., Klann, E., Blitzer, R. D., & Gouras, G. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012845 · Cited by 262 · see citing works
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Rey, N. L., Wesson, D. W., & Brundin, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.12.013 · Cited by 257 · see citing works
Self-citationSearcy, J. L., Phelps, J. T., Pancani, T., Kadish, I., Popovic, J., Anderson, K. L., Beckett, T. L., Murphy, M. P., Chen, K.-C., Blalock, E. M., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111661 · Cited by 154 · see citing works
Gravel, M., Béland, L.-C., Soucy, G., Abdelhamid, E., Rahimian, R., Gravel, C., & Kriz, J. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.0854-15.2016 · Cited by 117 · see citing works
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- Authors
- Wesson, D. W., Levy, E., Nixon, R. A., & Wilson, D. A.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- New York University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-01-13
- Volume
- 30
- Issue
- 2
- Pages
- 505-514
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2826174
- OpenAlex
- W1990300073
- Cited by
- 290
- References
- 56
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 23 · 2021: 29 · 2020: 10 · 2019: 18 · 2018: 16 · 2017: 15 · 2016: 17 · 2015: 16 · 2014: 27 · 2013: 22 · 2012: 19
- FWCI
- 12.87
- 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)
- Funders
- Alzheimer's Association
- National Institutes of Health (AG017617)
- National Institute on Aging (R01AG037693, AG017617, P01AG017617)
- National Institute on Deafness and Other Communication Disorders (DC-003906, R01DC003906)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, olfactory dysfunction, amyloid-beta, amyloid precursor protein, olfactory bulb, biomarkers, transgenic mouse model
- MeSH terms
- Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Discrimination, Psychological, Disease Models, Animal, Gene Expression Regulation, Habituation, Psychophysiologic, Humans, Mice, Transgenic, Odorants, Olfactory Pathways, Perceptual Disorders, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Olfactory Perception
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