U. Rüb and K. Farrag are joint first authors.
Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2)
Article first published online: 9 SEP 2013
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 39, Issue 6, pages 634–643, October 2013
How to Cite
Rüb, U., Farrag, K., Seidel, K., Brunt, E. R., Heinsen, H., Bürk, K., Melegh, B., von Gall, C., Auburger, G., Bohl, J., Korf, H. W., Hoche, F. and den Dunnen, W. (2013), Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2). Neuropathology and Applied Neurobiology, 39: 634–643. doi: 10.1111/nan.12025
W. den Dunnen and F. Hoche are joint senior authors.
- Issue published online: 9 SEP 2013
- Article first published online: 9 SEP 2013
- Accepted manuscript online: 30 JAN 2013 06:40AM EST
- Manuscript Accepted: 18 JAN 2013
- Manuscript Received: 18 JAN 2012
- ADCA-Vereniging Nederland
- Stiftung Hoffnung
- Dr. Senckenberg Stiftung
- basal forebrain;
- cholinergic system;
Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of attention, impairments of memory, as well as frontal-executive and visuospatial dysfunctions. As the possible morphological correlates of these cognitive SCA2 deficits are unclear we examined the cholinergic basal forebrain nuclei, which are believed to be crucial for several aspects of normal cognition and may contribute to impairments of cognitive functions under pathological conditions.
We studied pigment–Nissl-stained thick tissue sections through the cholinergic basal forebrain nuclei (that is, medial septal nucleus, nuclei of the diagonal band of Broca, basal nucleus of Meynert) of four clinically diagnosed and genetically confirmed SCA2 patients and of 13 control individuals according to the pathoanatomical approach. The pathoanatomical results were confirmed by additional quantitative investigations of these nuclei in the SCA2 patients and four age- and gender-matched controls.
Our study revealed a severe and consistent neuronal loss in all of the cholinergic basal forebrain nuclei (medial septal nucleus: 72%; vertical nucleus of the diagonal band of Broca: 74%; horizontal limb of the diagonal band of Broca: 72%; basal nucleus of Meynert: 86%) of the SCA2 patients studied. Damage to the basal forebrain nuclei was associated with everyday relevant cognitive deficits only in our SCA2 patient with an additional Braak and Braak stage V Alzheimer's disease (AD)-related tau pathology.
The findings of the present study: (1) indicate that the mutation and pathological process underlying SCA2 play a causative role for this severe degeneration of the cholinergic basal forebrain nuclei and (2) may suggest that degeneration of the cholinergic basal forebrain nuclei per se is not sufficient to cause profound and global dementia detrimental to everyday practice and activities of daily living.