The mechanisms underlying olfactory deficits in apolipoprotein E–deficient mice: focus on olfactory epithelium and olfactory bulb

Zhang, Jiajia; Hao, Caiyuan; Jiang, Jinxiang; Feng, Yangjian; Chen, Xi; Zheng, Ying; Liu, Jiawei; Zhang, Zhilin; Long, Cheng; Yang, Li

doi:10.1016/j.neurobiolaging.2017.09.036

Cited by 22 publications

(12 citation statements)

References 65 publications

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“…As mentioned in the introduction, evidence suggests that the number of mature olfactory sensory neurons in the olfactory epithelium is reduced in AD [65]. Therefore, future AD studies should focus on investigating the relationship between the reduced number of olfactory neurons at the periphery and the systems-level FC investigated in the current study.…”

Section: Limitations Of the Studymentioning

confidence: 89%

“…For example, using task fMRI, Vasavada et al (2017) suggested that olfactory deficits are most likely caused by degeneration in the central olfactory nervous system. Likewise, Zhang et al (2018) showed that the number of mature olfactory sensory neurons in the olfactory epithelium is reduced in apolipoprotein E (ApoE)-deficient mice and suggested a link between the olfactory mucosa (peripheral) and the pathogeneses of AD.…”

Section: Introductionmentioning

confidence: 99%

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Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Testa

Jordan

et al. 2019

Brain Sciences

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Olfactory impairment is associated with prodromal Alzheimer’s disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other temporal lobe structures. This selective vulnerability suggests that the functional connectivity (FC) between the olfactory network (ON), consisting of the POC, insula and orbital frontal cortex (OFC) (Tobia et al., 2016), and the hippocampus may be impaired in early stage AD. Yet, the development trajectory of this potential FC impairment remains unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate FC changes between the ON and hippocampus in four groups: aged-matched cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. FC was calculated using low frequency fMRI signal fluctuations in the ON and hippocampus (Tobia et al., 2016). We found that the FC between the ON and the right hippocampus became progressively disrupted across disease states, with significant differences between EMCI and LMCI groups. Additionally, there were no significant differences in gray matter hippocampal volumes between EMCI and LMCI groups. Lastly, the FC between the ON and hippocampus was significantly correlated with neuropsychological test scores, suggesting that it is related to cognition in a meaningful way. These findings provide the first in vivo evidence for the involvement of FC between the ON and hippocampus in AD pathology. Results suggest that functional connectivity (FC) between the olfactory network (ON) and hippocampus may be a sensitive marker for Alzheimer’s disease (AD) progression, preceding gray matter volume loss.

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Section: Limitations Of the Studymentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Testa

Jordan

et al. 2019

Brain Sciences

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“…Bottom, Apolipoprotein E deficiency alters the maturation of ORNs. All these alterations lead to deficits in olfactory-driven behaviors (Nathan et al, 2010;Zhang et al, 2018).…”

Section: Amyloid and Tau Cascadementioning

confidence: 99%

“…ApoE-knockout (KO) mice display a deficit in odorant responses recorded from the OE surface via electro-olfactograms (Zhang et al, 2018), which represent the summed generator potential recorded from multiple ORNs in the OE that are activated by an odorant. Hence, electro-olfactograms depend on the number of responsive ORNs in the OE and could also reflect the change of function of transduction proteins (Pinato et al, 2008;Song et al, 2008;Cygnar and Zhao, 2009;Cygnar et al, 2010).…”

Section: Electrophysiological Responses Of the Oe In Alzheimer's Diseasementioning

confidence: 99%

“…Hence, electro-olfactograms depend on the number of responsive ORNs in the OE and could also reflect the change of function of transduction proteins (Pinato et al, 2008;Song et al, 2008;Cygnar and Zhao, 2009;Cygnar et al, 2010). Apolipoprotein E-KO mice showed both a deficit in the amplitude of odorant responses and a lack of adaptation at ages 3-5 months (Zhang et al, 2018). To our knowledge, no further electrophysiological data are available of mouse models for AD.…”

Section: Electrophysiological Responses Of the Oe In Alzheimer's Diseasementioning

confidence: 99%

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Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

et al. 2020

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The sense of smell has been shown to deteriorate in patients with some neurodegenerative disorders. In Parkinson's disease (PD) and Alzheimer's disease (AD), decreased ability to smell is associated with early disease stages. Thus, olfactory neurons in the nose and olfactory bulb (OB) may provide a window into brain physiology and pathophysiology to address the pathogenesis of neurodegenerative diseases. Because nasal olfactory receptor neurons regenerate throughout life, the olfactory system offers a broad variety of cellular mechanisms that could be altered in AD, including odorant receptor expression, neurogenesis and neurodegeneration in the olfactory epithelium, axonal targeting to the OB, and synaptogenesis and neurogenesis in the OB. This review focuses on pathophysiological changes in the periphery of the olfactory system during the progression of AD in mice, highlighting how the olfactory epithelium and the OB are particularly sensitive to changes in proteins and enzymes involved in AD pathogenesis. Evidence reviewed here in the context of the emergence of other typical pathological changes in AD suggests that olfactory impairments could be used to understand the molecular mechanisms involved in the early phases of the pathology.

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Olfactory impairment in men and mice related to aging and amyloid-induced pathology

Tzeng

Figarella

Garaschuk

2021

Pflugers Arch - Eur J Physiol

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Olfaction, or the sense of smell, is one of the most ancient senses in men and mice, important for a large variety of innate and acquired behaviors. Clinical data reveal an early impairment of olfaction during normal aging and in the course of neurodegenerative diseases, but the underlying cellular/molecular mechanisms remain obscure. In the current review, we compare different aspects of the aging- and Alzheimer’s disease related impairment of olfaction in men and mice, aiming at the identification of common morbidities and biomarkers, which can be analyzed in detail in the appropriate mouse models. We also identify common, often interdependent (patho)physiological pathways, including but not limited to extracellular amyloid depositions, neuroinflammation, ɛ4 allele of the apolipoprotein E, CNS insulin resistance, and the impairment of adult neurogenesis, to be targeted by basic and clinical research.

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The mechanisms underlying olfactory deficits in apolipoprotein E–deficient mice: focus on olfactory epithelium and olfactory bulb

Cited by 22 publications

References 65 publications

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

Olfactory impairment in men and mice related to aging and amyloid-induced pathology

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