Neurodegeneration-Associated Proteins in Human Olfactory Neurons Collected by Nasal Brushing

Brozzetti, Lorenzo; Sacchetto, Luca; Cecchini, Maria Paola; Avesani, Anna; Perra, Daniela; Bongianni, Matilde; Portioli, Corinne; Scupoli, Maria Teresa; Ghetti, Bernardino; Monaco, Salvatore; Buffelli, Mario Rosario; Zanusso, Gianluigi

doi:10.3389/fnins.2020.00145

Cited by 37 publications

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“…While proving that Lewy bodies affect microtubule nucleation and cellular polarity in neurons of PD patients is likely to prove difficult, nasal brushing, a method to sample olfactory neurons from the epithelium ( Orru et al, 2014 ), might offer a route to analyse the olfactory cilia. Indeed, this process has been able to detect α-syn and other aggregating proteins involved in neurodegenerative diseases in olfactory neurons from patients ( Brozzetti et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Alpha synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome

et al. 2020

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Protein aggregates are the pathogenic hallmarks of many different neurodegenerative diseases and include the accumulation of α-synuclein, the main component of Lewy bodies found in Parkinson's disease. Aggresomes are closely-related, cellular accumulations of misfolded proteins. They develop in a juxtanuclear position, adjacent to the centrosome, the microtubule organizing centre of the cell, and share some protein components. Despite the long-standing observation that aggresomes/Lewy bodies and the centrosome sit side-by-side in the cell, no studies have been done to see whether these protein accumulations impede organelle function. We investigated whether the formation of aggresomes affected key centrosome functions: its ability to organize the microtubule network and to promote cilia formation. We find that when aggresomes are present, neuronal cells are unable to organise their microtubule network. New microtubules are not nucleated and extended, and the cells fail to respond to polarity cues. Since neurons are polarised, ensuring correct localisation of organelles and the effective intracellular transport of neurotransmitter vesicles, loss of centrosome activity could contribute to functional deficits and neuronal cell death in Parkinson's disease. In addition, we provide evidence that many cell types, including dopaminergic neurons, cannot form cilia when aggresomes are present, which would affect their ability to receive extracellular signals.

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Section: Discussionmentioning

confidence: 99%

Alpha synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome

et al. 2020

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“…In postmortem tissues from AD patients, both Aβ plaques and NFTs are found in both OE and OB (Talamo et al, 1989). Amyloid-β and tau expression can also be found in cells swabbed from the nasal cavity of healthy human subjects (Brozzetti et al, 2020).…”

Section: Olfaction and Alzheimer's Diseasementioning

confidence: 99%

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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“…Furthermore, the prion-like hypothesis in AD is also worth noting concerning the olfactory impairment. Like the prion detected in olfactory epithelium of sporadic Creutzfeldt-Jakob disease (Tabaton et al, 2004), Aβ and tau also appeared in olfactory structures in AD and healthy subjects, including olfactory epithelium and OB (Kovacs et al, 1999;Wilson et al, 2007;Arnold et al, 2010;Brozzetti et al, 2020), both are susceptible to protein and enzyme modifications involved in AD pathogenesis (Dibattista et al, 2020). It was hypothesized that pathological modifications lead to the activation of protein accumulation in the OB after environmental insults, and then induces the propagation of the disease within the brain in a prionlike fashion by a templating process (Rey et al, 2018).…”

Section: Discussionmentioning

confidence: 97%

Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis

Fan

et al. 2020

Front. Neurosci.

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Background: The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear.Objective: This meta-analysis aimed to examine the associations between OI and Aβ and tau burden.Methods: Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aβ or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups.Results: Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aβ PET, one involved tau PET (N = 26), and four involved CSF Aβ or tau (N = 345). OI was negatively associated with Aβ PET in the mixed (r = −0.25, P = 0.008) and cognitively normal groups (r = −0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aβ42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET.Conclusion: The associations between OI ability and Aβ and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.

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Neurodegeneration-Associated Proteins in Human Olfactory Neurons Collected by Nasal Brushing

Cited by 37 publications

References 50 publications

Alpha synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome

Alpha synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome

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

Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis

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