title: Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders.
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.
authors.affiliation: Laboratory of Regenerative Therapy, Neuroscience Division, CIMA and Department of Neurology, Clínica Universidad de Navarra, Pamplona, Avenida de Pío XII 36, 31008, Pamplona, Spain.
authors.forename: Iñaki-Carril
authors.initials: IC
authors.lastname: Mundiñano
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Caballero
authors.forename: Cristina
authors.initials: C
authors.lastname: Ordóñez
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez
authors.forename: Carla
authors.initials: C
authors.lastname: DiCaudo
authors.forename: Irene
authors.initials: I
authors.lastname: Marcilla
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Erro
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Tuñon
authors.forename: Maria-Rosario
authors.initials: MR
authors.lastname: Luquin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001344:Autopsy; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D057180:Frontotemporal Dementia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins; D004298:Dopamine