Acta Neuropathologica

, Volume 126, Issue 3, pp 411–425 | Cite as

Reduced cholinergic olfactory centrifugal inputs in patients with neurodegenerative disorders and MPTP-treated monkeys

  • Iñaki-Carril Mundiñano
  • Maria Hernandez
  • Carla DiCaudo
  • Cristina Ordoñez
  • Irene Marcilla
  • Maria-Teresa Tuñon
  • Maria-Rosario LuquinEmail author
Original Paper


Olfactory impairment is a common feature of neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Olfactory bulb (OB) pathology in these diseases shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. Since cholinergic denervation might be a common underlying pathophysiological feature, the objective of this study was to determine cholinergic innervation of the OB in 27 patients with histological diagnosis of PD (n = 5), AD (n = 14), DLB (n = 8) and 8 healthy control subjects. Cholinergic centrifugal inputs to the OB were clearly reduced in all patients, the most significant decrease being in the DLB group. We also studied cholinergic innervation of the OB in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (n = 7) and 7 intact animals. In MPTP-monkeys, we found that cholinergic innervation of the OB was reduced compared to control animals (n = 7). Interestingly, in MPTP-monkeys, we also detected a loss of cholinergic neurons and decreased dopaminergic innervation in the horizontal limb of the diagonal band, which is the origin of the centrifugal cholinergic input to the OB. All these data suggest that cholinergic damage in the OB might contribute, at least in part, to the olfactory dysfunction usually exhibited by these patients. Moreover, decreased cholinergic input to the OB found in MPTP-monkeys suggests that dopamine depletion in itself might reduce the cholinergic tone of basal forebrain cholinergic neurons.


Olfactory bulb Parkinson’s disease Alzheimer’s disease Dementia with Lewy bodies Cholinergic system MPTP Monkey 



Alzheimer’s disease


Anterior olfactory nucleus


Choline acetyl transferase


Choline acetyl transferase immunoreactivity/immunoreactive


Dementia with Lewy bodies


External plexiform layer


Granule cell layer


Glomerular layer


Horizontal limb of the diagonal band of Broca


Internal plexiform layer




Nucleus basalis of Meynert


Olfactory bulb


Phosphate buffer saline


Parkinson’s disease




Standard error of the mean


Substantia nigra


Tyrosine hydroxylase


Tyrosine hydroxylase immunoreactivity/immunoreactive

Tris HCl

2-Amino-2-hydroxymethyl-propane-1,3-diol hydrochloride


Ventral tegmental area



This study was supported by the UTE-project/Foundation for Applied Medical Research (FIMA). The authors thank Monica Kurtis for English edition of the manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Iñaki-Carril Mundiñano
    • 1
    • 2
  • Maria Hernandez
    • 1
    • 2
  • Carla DiCaudo
    • 1
    • 2
  • Cristina Ordoñez
    • 1
    • 2
  • Irene Marcilla
    • 1
    • 2
  • Maria-Teresa Tuñon
    • 3
  • Maria-Rosario Luquin
    • 1
    • 2
    Email author
  1. 1.Laboratory of Regenerative Therapy, Neuroscience DivisionCIMAPamplonaSpain
  2. 2.Department of NeurologyClínica Universidad de NavarraPamplonaSpain
  3. 3.Complejo Hopitalario de Navarra, Banco de Tejidos Neurológicos de NavarraPamplonaSpain

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