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Alzheimer's Disease Research
Completed Award

Dr. Michael Rohe

Michael Rohe, Ph.D.

Max-Delbrueck Center for Molecular Medicine
Berlin, Germany

Title: Role of SORLA in Transport of TrkB and APP in Alzheimer's Disease
Non-Technical Title: Role of the Neuronal Receptor SORLA in Transport of TrkB and APP in Alzheimer's Disease

Thomas E. Willnow, Ph.D.
Max-Delbrueck Center for Molecular Medicine

Duration: July 1, 2011 - June 30, 2013
Award Type: Postdoctoral Fellowship
Award Amount: $100,000


Accelerated amyloidogenic processing of APP and insufficient trophic signals from BDNF are two well-documented risk factors in AD. Intriguingly, both pathways converge on yet another established AD risk gene, the neuronal sorting receptor SORLA. A more detailed understanding of how these pathways are interconnected in the healthy and in the diseased brain will provide the basis for evaluating the therapeutic potential of SORLA to reduce neurotoxicity (caused by too much Abeta) and to strengthen neurotrophic support (caused by poor BDNF signals).


The protein called SORLA was identified as a risk factor in Alzheimer's disease. It helps with the production of beta-amyloid which forms the characteristic plaques in Alzheimer's disease. Abnormally high levels of beta-amyloid cause the death of nerve cells in patients, leading to dementia. Recently, Drs. Michael Rohe, Thomas Willnow, and collaborators have identified the protective factor BDNF to activate SORLA. Regulation of SORLA by BDNF reduces the amount of beta-amyloid. An abnormally low level of BDNF is associated with Alzheimer's disease, because this causes low levels of SORLA that then leads to high levels of toxic beta-amyloid. Beta-amyloid is produced from the protein APP, and BDNF exerts its protective function through binding to the protein TrkB. Both APP and TrkB are bound by SORLA that is thought to control their transport within the cell.

To sort out this complicated interaction of proteins, Dr. Rohe and collaborators will find out exactly how SORLA works in concert with APP and TrkB. Their discoveries could potentially lead to a new disease-modifying treatment designed to increase the levels of SORLA in the brain in order to prevent the release of beta-amyloid and stop plaque formation.


Hartl, D., Schuldt, V., Forler, S., Zabel, C., Klose, J., Rohe, M. (2012). "Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease." Journal of Proteome Research, 2012 11 (6), 3295-3304 PubMed Icon Google Scholar Icon

Rohe M, Hartl D, Fjorback AN, Willnow TE (2013) SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF. PLoS One, accepted for publication. PubMed Icon Google Scholar Icon

Hartl D#, Klatt S, Roch M, Konthur Z, Klose J, Willnow TE, and Rohe M (2013) Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons. PLoS One, 8(6):e65920. PubMed Icon Google Scholar Icon

Progress Updates:

Two well-documented risk factors in Alzheimer's disease (AD) are accelerated breakdown of the APP protein into beta-amyloid (Abeta), and insufficient support for nerve cells from the protective protein, called BDNF. Intriguingly, both pathways converge on yet another established AD risk gene that produces the neuronal sorting receptor protein, called SORLA. A more detailed understanding of how these pathways are interconnected in the healthy and in the diseased brain is the major aim of this project. Dr. Rohe’s team is evaluating the therapeutic potential of SORLA to reduce toxicity for neurons (caused by too much Abeta) and to reinstate support of neurons (caused by poor BDNF signals).

So far, Dr. Rohe’s team was able to document that SORLA not only regulates the breakdown of APP but also the transport of the BDNF receptor, called TrkB. Binding of BDNF to TrkB is central for supporting the function and survival of neurons. Because of the impaired transport of TrkB, BDNF signals received by neurons lacking SORLA are reduced. This reduction renders affected neurons vulnerable and disrupts their proper function. In support of this hypothesis, Dr. Rohe identified that SORLA deficiency disrupts the function of several brain proteins that are important for proper communication between nerve cells. Intriguingly, the disruption of these proteins coincided with impaired learning and memory in SORLA-deficient mice, further underscoring the relevance of this signaling pathway for cognitive functions. Since low levels of SORLA have been documented in AD patients, Dr. Rohe’s data provide an explanation of how low levels of the receptor protein may translate into memory deficits.

Investigator Biography:

Dr. Michael Rohe is currently working as a senior postdoctoral fellow at the Max-Delbrueck Center for Molecular Medicine in Berlin. He attained a doctorate in Biology at the Free University of Berlin in 2008. Earlier he had graduated with a degree in Biology at the Ludwig Maximilian University of Munich in 2004. During his studies he also worked as an undergraduate at the Max Planck Institute of Neurobiology in Martinsried.