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Central cholinergic dysfunction in the adult form of Niemann Pick disease type C: a further link with Alzheimer’s disease?

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Abstract

Adult patients with Niemann-Pick disease type C (NPC) usually develop cognitive impairment progressing to dementia, whose pathophysiology remains still unclear. Noteworthy parallels exist in cognitive impairment and cellular pathology of NPC and Alzheimer’s disease (AD). In particular, alterations of cholinergic system, which represent one of the pathological hallmarks and contribute to cognitive deterioration in AD, have recently been demonstrated in a human brain autopsy and in an experimental model of NPC. This finding raised the issue that central cholinergic circuits dysfunction may contribute to pathophysiology of cognitive impairment in NPC as well, and prompted us to evaluate the cholinergic functional involvement in NPC patients by applying a neurophysiologic technique, named short-latency afferent inhibition (SAI). We describe clinical, biochemical, molecular and neuropsychological features, and SAI findings in three patients affected by NPC. Diagnosis of NPC was assessed by molecular analysis of the NPC1 gene in all patients. In two of them, biochemical analysis of intracellular accumulation of unesterified cholesterol was also performed. The main clinical features were cerebellar ataxia, vertical supranuclear gaze palsy and a variable degree of cognitive impairment ranging from only memory impairment to severe dementia. Electrophysiological evaluation revealed a reduced SAI in all three patients. Our SAI findings provide evidence of cholinergic dysfunction in patients with the adult form of NPC, supporting that cholinergic alterations may play a role in cognitive impairment in NPC, and strengthening the similarities between NPC and AD.

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Acknowledgments

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy

    Fiore Manganelli, Raffaele Dubbioso, Rosa Iodice, Antonietta Topa, Cinzia Valeria Russo, Lucia Ruggiero, Stefano Tozza, Alessandro Filla & Lucio Santoro

  2. Regional Coordinator Centre for Rare Diseases, University Hospital “Santa Maria della Misericordia”, Udine, Italy

    Andrea Dardis

Authors
  1. Fiore Manganelli
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  2. Raffaele Dubbioso
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  3. Rosa Iodice
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  4. Antonietta Topa
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  5. Andrea Dardis
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  6. Cinzia Valeria Russo
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  7. Lucia Ruggiero
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  8. Stefano Tozza
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  9. Alessandro Filla
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  10. Lucio Santoro
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Corresponding author

Correspondence to Lucio Santoro.

Additional information

F. Manganelli and R. Dubbioso equally contributed to this work.

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Manganelli, F., Dubbioso, R., Iodice, R. et al. Central cholinergic dysfunction in the adult form of Niemann Pick disease type C: a further link with Alzheimer’s disease?. J Neurol 261, 804–808 (2014). https://doi.org/10.1007/s00415-014-7282-2

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  • DOI: https://doi.org/10.1007/s00415-014-7282-2

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