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Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders

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Abstract

Olfactory dysfunction is a frequent and early feature of patients with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) and is very uncommon in patients with frontotemporal dementia (FTD). Mechanisms underlying this clinical manifestation are poorly understood but the premature deposition of protein aggregates in the olfactory bulb (OB) of these patients might impair its synaptic organization, thus accounting for the smell deficits. Tau, β-amyloid and alpha-synuclein deposits were studied in 41 human OBs with histological diagnosis of AD (n = 24), PD (n = 6), FTD (n = 11) and compared with the OB of 15 control subjects. Tau pathology was present in the OB of all patients, irrespective of the histological diagnosis, while β-amyloid and alpha-synuclein protein deposit were frequently observed in AD and PD, respectively. Using stereological techniques we found an increased number of dopaminergic periglomerular neurons in the OB of AD, PD and FTD patients when compared with age-matched controls. Moreover, volumetric measurements of OBs showed a significant decrease only in AD patients, while the OB volume was similar to control in PD or FTD cases. The increased dopaminergic tone created in the OBs of these patients could reflect a compensatory mechanism created by the early degeneration of other neurotransmitter systems and might contribute to the olfactory dysfunction exhibited by patients with neurodegenerative disorders.

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Acknowledgments

This study was supported by the Government of Navarra (Ref Go Na46/07) and by the UTE-project/Foundation for Applied Medical Research (FIMA).

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  1. Laboratory of Regenerative Therapy, Neuroscience Division, CIMA and Department of Neurology, Clínica Universidad de Navarra, Pamplona, Avenida de Pío XII 36, 31008, Pamplona, Spain

    Iñaki-Carril Mundiñano, Cristina Ordóñez, Maria Hernandez, Carla DiCaudo, Irene Marcilla & Maria-Rosario Luquin

  2. Banco de Tejidos Neurológicos de Navarra, Centro de Investigación Biomédica, Hospital de Navarra, Irunlarrea 3, 31008, Pamplona, Spain

    Maria-Cristina Caballero, Maria-Elena Erro & Maria-Teresa Tuñon

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  1. Iñaki-Carril Mundiñano
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Mundiñano, IC., Caballero, MC., Ordóñez, C. et al. Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol 122, 61–74 (2011). https://doi.org/10.1007/s00401-011-0830-2

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