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Will biomarkers help in the detection of Pick’s disease?

Pick’s disease, which is commonly seen in old-aged people, basically comes under the group of frontotemporal dementia disorders. Most frequently, this condition has an impact on a person's behavior, but it can also interfere with their capacity for communication. Although there is no known cure for this condition, symptoms can be managed by administering certain drugs commonly used for neurodegenerative disorders. As this disease spectrum closely resembles other age related diseases like Alzheimer’s disease, dementia with Lewy bodies, etc; the differential diagnosis of this condition should be ruled out. Biomarkers help in the accurate diagnosis of the disease [1].


What are the diagnostic methods for Pick’s disease?


There are numerous tests available to identify Pick’s disease. They consist of the following:

  • Recording personal and familial history in detail.

  • Neurological examination

  • Cognitive and behavioral tests

  • Computerized tomography (CT )

  • Electroencephalogram (EEG)

  • Genetic analysis

  • Magnetic resonance imaging (MRI)

  • Positron emission tomography (PET)

However, all these tests will only provide the tentative diagnosis of frontotemporal dementia disorders (a group of disorders that includes Pick’s disease), but cannot rule out the differential diagnosis such as Alzheimer’s disease which can be done with the help of biomarkers [2].


What are biomarkers?


A molecular, cellular or biochemical change that can be precisely and repeatedly measured is referred to as a biomarker. Biomarkers are used to recognize and track pathological and physiological processes as well as responses to pharmacological interventions.


Pick’s disease

Genes, DNA, RNA, platelets, enzymes, hormones, and other biomolecules such as carbohydrates, proteins and lipids are examples of biomarkers. A biomarker can be any substance that aids in the diagnosis of a condition, including metabolites, modifications to biological processes or structures, or distinguishing characteristics. There are numerous ways to categorize biomarkers [3].


How do they help in the identification of Pick’s disease?

  • Biomarkers can be collected from either cerebrospinal fluid (CSF) or blood for the diagnosis of Pick’s disease. Collecting them from blood is the preferred method as it is a less invasive procedure and eliminates the lumbar puncture procedure (process to collect CSF).

  • Other advantages of collecting biomarkers from blood are its low cost, and the procedure can be repeated if required to monitor the progression of the disease. Also, they may be used for purposes other than diagnosis, such as screening for families of patients with familial history of Pick’s disease or evaluating the efficacy of a potential treatment.

  • Neurofilament light chain protein (NFL) - according to literature, is detected in the majority of cases of frontotemporal dementias which helps to rule out the presence of Alzheimer’s disease. Can be collected from both blood and CSF.

  • Transactive response DNA-binding protein (TDP-43) - nevertheless, there is no concrete evidence that TDP-43 levels are more common in Pick’s disease patients than in Alzheimer’s disease patients. Although more phosphorylated TDP-43 has been found in the plasma of Pick’s disease patients than in Alzheimer’s patients according to a few studies, however more research is needed.

  • Plasma tau - numerous studies have measured plasma tau levels. Although it is unrelated to Alzheimer’s disease or frontotemporal dementia, elevated plasma total tau levels may be associated with cognitive impairment.

  • Progranulin - mutations in the progranulin gene (GRN) account for about 20% of the familial type of Pick’s disease. Blood or CSF can be used to measure progranulin. Progranulin levels in plasma or serum have frequently been measured in these patients with GRN mutations. According to the current findings, progranulin levels appear to be helpful in distinguishing GRN mutation carriers from other mutation carriers.

All these biomarkers will help to differentiate Pick’s disease from Alzheimer’s disease which has the same clinical findings as Pick’s disease, and helps in the early diagnosis of the disease [4].


Biomarkers will boost the process of diagnosis!


Biomarkers are definitely a useful tool in differentiating Pick’s disease from other disorders which have the same clinical features. But the ultimate diagnosis of Pick’s disease can be confirmed only by the presence of Pick bodies in the brain tissue, which is done by the histopathological examination of the biopsy specimen. Further studies are required in the development of new biomarkers that can discriminate Pick’s disease from other diseases.


References


1. M. M. Pippin and V. Gupta, Pick Disease,” in StatPearls, Treasure Island (FL): StatPearls Publishing, 2022. Accessed: Dec. 30, 2022. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK562226/

2. R. M. Tsai and A. L. Boxer, “Treatment of Frontotemporal Dementia,” Curr Treat Options Neurol, vol. 16, no. 11, p. 319, Nov. 2014, doi: 10.1007/s11940-014-0319-0.

3. I. J. Swift et al., “Fluid biomarkers in frontotemporal dementia: past, present and future,J Neurol Neurosurg Psychiatry, vol. 92, no. 2, pp. 204–215, Feb. 2021, doi: 10.1136/jnnp-2020-323520.

4. S. Ntymenou et al., “Blood Biomarkers in Frontotemporal Dementia: Review and Meta-Analysis,” Brain Sci, vol. 11, no. 2, p. 244, Feb. 2021, doi: 10.3390/brainsci11020244.

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Collaborators

IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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