Front. Neurol., 11 July 2011 |

Brainstem: neglected locus in neurodegenerative diseases

  • 1 Department of Neurology, Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA
  • 2 Brazilian Aging Brain Study Group-LIM 22, Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil
  • 3 Dr. Senckenberg Chronomedical Institute, Goethe-University, Frankfurt/Main, Germany
  • 4 Laboratory of Morphological Brain Research, Psychiatrics Clinics, University of Wuerzburg, Wuerzburg, Germany

The most frequent neurodegenerative diseases (NDs) are Alzheimer’s disease (AD), Parkinson’s disease (PD), and frontotemporal lobar degeneration associated with protein TDP-43 (FTLD–TDP). Neuropathologically, NDs are characterized by abnormal intracellular and extra-cellular protein deposits and by disease-specific neuronal death. Practically all terminal stages of NDs are clinically associated with dementia. Therefore, major attention was directed to protein deposits and neuron loss in supratentorial (telencephalic) brain regions in the course of NDs. This was also true for PD, although the pathological hallmark of PD is degeneration of pigmented neurons of the brainstem’s substantia nigra (SN). However, PD pathophysiology was explained by dopamine depletion in the telencephalic basal ganglia due to insufficiency and degeneration of the projection neurons located in SN. In a similar line of argumentation AD- and FTLD-related clinical deficits were exclusively explained by supratentorial allo- and neo-cortical laminar neuronal necrosis. Recent comprehensive studies in AD and PD early stages found considerable and unexpected involvement of brainstem nuclei, which could have the potential to profoundly change our present concepts on origin, spread, and early clinical diagnosis of these diseases. In contrast with PD and AD, few studies addressed brainstem involvement in the course of the different types of FTLD–TDP. Some of the results, including ours, disclosed a higher and more widespread pathology than anticipated. The present review will focus mainly on the impact of brainstem changes during the course of the most frequent NDs including PD, AD, and FTLD–TDP, with special emphasis on the need for more comprehensive research on FTLDs.

Keywords: brainstem, human, pathology, neurodegenerative diseases, dementia, Alzheimer’s disease, frontotemporal lobar degeneration, Parkinson’s disease

Citation: Grinberg LT, Rueb U and Heinsen H (2011) Brainstem: neglected locus in neurodegenerative diseases. Front. Neur. 2:42. doi: 10.3389/fneur.2011.00042

Received: 04 March 2011; Paper pending published: 13 April 2011;
Accepted: 13 June 2011; Published online: 11 July 2011.

Edited by:

Martin Rhys Farlow, Indiana University School of Medicine, USA

Reviewed by:

Stefano F. Cappa, Vita-Salute San Raffaele University, Italy
Richard Mohs, Eli Lilly and Company, USA

Copyright: © 2011 Grinberg, Rueb and Heinsen. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Helmut Heinsen, Laboratory of Morphological Brain Research, University of Wuerzburg, Oberdürrbacher Strasse 6, 97080 Wuerzburg, Germany. e-mail: