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Olfactory dysfunction: its early temporal relationship and neural correlates in the pathogenesis of Alzheimer’s disease
Abstract
We interact with the physical world through our senses, and these aid our behavioral performance and various activities of life. Sensory information is transmitted in neuronal networks, and the brain optimally interprets the external and internal milieu/environment. This paper delineates the framework in which the pathogenesis of memory and cognitive dysfunction is underpinned by sensory olfactory dysfunction. ERC is the gateway for olfactory input to the hippocampus, and there is seamless synchronization between sensory function and hippocampal activity. Transmission of olfactory information to the hippocampus is sequential-it is projected from the olfactory receptors to olfactory bulb to the primary olfactory cortex (comprised the anterior olfactory nucleus, the olfactory tubercle, and the piriform cortex) to the entorhinal cortex (ERC). Through perforant pathway ERC enables olfactory inputs to effectively excite hippocampal neurons. One of the earliest pathological changes in Alzheimer's disease (AD) include the olfactory dysfunction and the atrophy in ERC and hippocampus (rate in ERC is higher than in the hippocampus). Olfactory dysfunction negatively impacts the ERC and the deafferenting of the hippocampus from olfactory inputs upregulates memory decline. Olfactory dysfunction, therefore, is an important and early correlate of AD pathology. A number of factors described here may cause olfactory dysfunction; this may lead to hypoperfusion, hypometabolism, impaired synaptic transmission, and variable atrophy in olfaction-related regions. Improvement in olfactory function, therefore, is an important goal in order to attenuate cognitive neuropathology in aging and AD. This article seeks to provide a comprehensive and balanced overview of olfactory neuropathology in incipient AD, and suggests strategies to enhance olfactory function and ameliorate cognitive decline.
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“the connection to the entorhinal cortex, the olfactory bulb, is directly affected by changes in the perforant pathway, and one of the earliest pathological changes in AD”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [49]
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Research works printed but not linked: 1
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Daulatzai, M. A. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23777 · Cited by 440
Self-citationThe olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases
Rey, N. L., Wesson, D. W., & Brundin, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.12.013 · Cited by 257
Daulatzai, M. A. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23634 · Cited by 222
Self-citationAAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 176
Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management
Kondo, K., Kikuta, S., Ueha, R., Suzukawa, K., & Yamasoba, T. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00208 · Cited by 154
Metadata
- Authors
- Daulatzai, M. A.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Daulatzai, Mak Adam
- Venue
- Journal of Neural Transmission
- Published
- 2015-05-06
- Volume
- 122
- Issue
- 10
- Pages
- 1475-1497
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W215713836
- Cited by
- 63
- References
- 359
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 5 · 2015: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- olfactory dysfunction, Alzheimer's disease, entorhinal cortex, hippocampus, perforant path, olfactory bulb, piriform cortex, anterior olfactory nucleus, olfactory tubercle, deafferentation, memory decline, cognitive decline, early biomarkers
- MeSH terms
- Alzheimer Disease, Animals, Olfaction Disorders, Brain, Humans, Disease Progression, Olfactory Perception
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