Leader: Francesca Cavalcanti (CNR); Other collaborator(s): Luigi Citrigno, Beatrice Greco.
We plan to exploit our ongoing collection of biological samples (peripheral blood, urine) from healthy subjects (ages 20 - 80) and from patients with aging-related neurological diseases (AD, PD, HD), to:
Brief description of the activities and of the intermediate results: In the period January March 2024, DNA samples from patients with Alzheimer's disease were assembled for the analysis of the methylation profile using the Epic array method based on bisulfite conversion and Illumina technology. The first test run was performed to test the quality of the DNA samples. Quantitative qPCR analysis of copy number variants of mitochondrial DNA (mtDNA-CN) from peripheral blood was performed on an initial number of the same samples.
In the period April-June 2024, the preparation of the 168 total DNA samples from patients affected by Alzheimer's disease to be subjected to the Epic array methylation analysis vs. a control population, in collaboration with Unical, was completed. The first results have been analyzed and the methylation analysis of the entire sample of 168 AD DNA is underway. The same population of 168 AD DNA samples has been subjected to quantitative analysis by qPCR of the number of copies of the mitochondrial DNA mtDNA-CN. The data from the quantitative analysis are being processed. During the quarter of activity, a review on the role of mtDNA-CN in age-related neurodegenerative disorders has been drafted, which has recently been published. During the quarter of activity, a collaborative study was conducted to analyze telomere length in a DNA sample from subjects affected by Friedreich's Ataxia and the results were submitted for publication in a Neurology journal.
The EPIC analysis of AD samples and controls, in collaboration with UniCal, has proceeded as planned. Data on the quantitation of mitochondrial DNA copies in 168 AD samples compared to controls were also analyzed. The results are being submitted for publication. In addition, the results of the study of telomere length in a DNA sample from subjects affected by Friedreich's Ataxia (FRDA) were published in the journal Movement Disorders. This study indicates that the analysis of telomere length in FRDA may be a relevant biomarker to follow the stages of this brain degenerative disease.
The analysis of data resulting from the EPIC study of AD samples (in collaboration with Unical) was started during the period October-December 2024. Furthermore DNA sampling from subjects with AD continued for the analysis of the role of mitochondrial DNA copy number in neurodegenerative disease.
Cerantonio A., Citrigno L., Greco B.M., De Benedittis S., Passarino G., Maletta R., Qualtieri A., Montesanto A., Spadafora P., Cavalcanti F The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions Int. J. Mol. Sci. 2024, 25, 6062. https://doi.org/10.3390/ijms25116062
Scarabino D., Veneziano L., Nethisinghe S., Mantuano E., Fiore A., Granata G., Solanky N. , Zanni G., Cavalcanti F., Corbo R.M., Giunti P. Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia. Mov Disord. 2024 Sep 5. https://doi.org/10.1002/mds.29976
Cerantonio A.; Citrigno L.; Bruno F.; Maletta R.; Greco B.M.; Montesanto A.; Passarino G.; Spadafora P.; Qualtieri A.; De Benedittis S.; Cavalcanti F. Mitochondrial DNA copy number in age-related neurodegenerative diseases: preliminary analysis from South Italy late-onset Alzheimer disease patients. XXVII Congresso Nazionale SIGU, Padova 2-4 ottobre 2024