Acta Neuropathologica

, Volume 119, Issue 6, pp 723–735 | Cite as

α-Synucleinopathy in the human olfactory system in Parkinson’s disease: involvement of calcium-binding protein- and substance P-positive cells

  • Isabel Ubeda-Bañon
  • Daniel Saiz-Sanchez
  • Carlos de la Rosa-Prieto
  • Lucia Argandoña-Palacios
  • Susana Garcia-Muñozguren
  • Alino Martinez-Marcos
Original Paper


Hyposmia is an early symptom of idiopathic Parkinson’s disease but the pathological bases of such dysfunction are largely unknown. The distribution of α-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by α-synucleinopathy were investigated in the olfactory system in Parkinson’s disease. Immunohistochemical distribution of α-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson’s disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. α-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by α-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that α-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by α-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.


α-Synuclein Lewy body Immunohistochemistry Olfactory Parkinson Hyposmia 



Nucleus accumbens


Anterior olfactory nucleus


Bulbar anterior olfactory nucleus


Cortical anterior lateral anterior olfactory nucleus


Cortical anterior medial anterior olfactory nucleus


Cortical posterior lateral anterior olfactory nucleus


Cortical posterior medial anterior olfactory nucleus


Intrapeduncular anterior olfactory nucleus


Retrobulbar anterior olfactory nucleus


Basolateral amygdala


Basomedial amygdala




Central amydala




Entorhinal cortex


External plexiform layer


Glomerular layer


Granule cell layer


Idiopathic Parkinson’s disease


Medial amgydala


Main olfactory bulb


Medial olfactory radiation




Olfactory radiation


Outer nerve layer


Olfactory peduncle


Olfactory tract


Periamygdaloid cortex


Parkinson’s disease


Piriform cortex


Posteromedial orbital lobule






Stratum album


Straight gyrus




Substance P




Tyrosine hydroxylase

Supplementary material

401_2010_687_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 36 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Isabel Ubeda-Bañon
    • 1
  • Daniel Saiz-Sanchez
    • 1
  • Carlos de la Rosa-Prieto
    • 1
  • Lucia Argandoña-Palacios
    • 2
  • Susana Garcia-Muñozguren
    • 2
  • Alino Martinez-Marcos
    • 1
  1. 1.Laboratorio de Neuroanatomía Humana, Facultad de Medicina/Centro Regional de Investigaciones BiomédicasUniversidad de Castilla-La ManchaAlbaceteSpain
  2. 2.Servicio de NeurologíaComplejo Hospitalario UniversitarioAlbaceteSpain

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