Annakaisa Haapasalo

Skin Cells May Provide Biomarker for Frontotemporal Dementia Diagnosis Interview with:

Annakaisa Haapasalo

Dr. Haapasalo

Annakaisa Haapasalo, PhD
Adjunct Professor
Research Director (Associate Professor
A.I. Virtanen Institute for Molecular Sciences
Molecular Neurodegeneration
University of Eastern Finland | UEF | What is the background for this study? At what age might these changes be present?

Response: Our research team is interested in understanding the underlying disease mechanisms and developing biomarkers for frontotemporal dementia (FTD). FTD is the second most common cause of dementia in the working age population. Presently, no efficient therapies exist for FTD, it is challenging to diagnose, and the disease mechanisms of different types of FTD remain largely unclear. We are especially interested in FTD associated with the C9orf72 repeat expansion because it is the most common genetic cause of frontotemporal dementia and exceptionally prevalent in Finnish FTD patients.

Many current studies of FTD and C9orf72 repeat expansion have largely concentrated on examining neurons, as these are the principle CNS cells that are affected in neurodegeneration. Neurons are also one of our key research interests, but obtaining neurons directly from living patients is difficult in many ways. Therefore, we became interested in exploring the FTD patient skin fibroblasts with the idea in mind that they might represent more easily accessible patient-derived cells than neurons for trying to decipher disease mechanisms of FTD. Moreover, we were interested in finding out if these cells show any specific alterations or deficiencies that could be utilized later on in biomarker studies or testing drug effects. What are the main findings?

Response: The main findings of our study were the significantly increased accumulation of vesicles containing a protein termed p62 as well as the defective mitochondrial energy metabolism in the frontotemporal dementia patient fibroblasts when compared to the fibroblasts from healthy donors. It was interesting that these changes were not detected only in the fibroblasts of the C9orf72 repeat expansion carriers but also in fibroblasts from sporadic FTD patients. Therefore, they appear to be changes detectable in FTD patients’ fibroblasts in general and not linked specifically to only  the C9orf72 repeat expansion.

The age of the patients participating in this study varied between 53 and 77 years of age, but we do not yet know how early it would be possible to detect these changes in the FTD patient skin fibroblasts. What should readers take away from your report?

Response: We found it interesting that the changes observed in the skin fibroblasts are partially similar to those observed in the brain and neurons of frontotemporal dementia patients. Because brain cells can rarely be obtained from the brains of living patients, other patient-derived cells, such as skin fibroblasts, may help clarifying disease mechanisms at the cellular and molecular level and prove useful in biomarker or drug research, even at the individual level. In addition, patient-derived skin fibroblasts can be used  as sources for producing induced pluripotent stem cells (iPSCs), which in turn can be further differentiated to different types of brain cells, such as neurons, and used as human disease models in research. We are currently also performing studies in the iPSC-derived neurons from FTD patients and looking if we see similar alterations in them. What recommendations do you have for future research as a result of this work? 

Response: It might be interesting to assess next whether the now detected cellular changes could be utilized in biomarker studies or as endpoints in e.g. testing of drug effects. Also, it is important to investigate if the accumulation of p62 vesicles is specific only to FTD patient fibroblasts or is it detectable also in patients with other neurodegenerative diseases. If it was FTD patient-specific, it is possible that it might be employed as a biomarker for these patients, but clarifying this will need further investigations.

I don’t have any disclosures.


Leskelä, S., Hoffmann, D., Rostalski, H. et al. FTLD Patient–Derived Fibroblasts Show Defective Mitochondrial Function and Accumulation of p62. Mol Neurobiol (2021).



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Last Updated on August 15, 2021 by Marie Benz MD FAAD