Project Description

Identification and validation of novel cell-free dna methylation-based biomarkers for diagnosis of alzheimer’s disease and frontotemporal dementia and disease progression in blood

Carolina Ochoa Rosales | Universidad Adolfo Ibanez; Hieab H. Adams, PhD; Claudia Duran-Aniotz, PhD; Agustin Ibanez, PhD
Competition Sponsor
: Chile Agencia Nacional de Investigacion y Desarrollo
Awardee Year: 2023

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are prevalent forms of dementia characterized by specific brain region degeneration, causing cognitive and functional decline. Unfortunately, current diagnostic methods often detect these conditions too late for effective intervention. To address this, our project proposes a groundbreaking approach utilizing epigenetic marks of methylation in cell-free DNA (cfDNAm), in order to pinpoint degeneration in affected brain regions. We hypothesize that unique patterns of neurodegeneration seen in AD and FTD can be traced in peripheral blood using cfDNAm. This novel biomarker can serve as a barcode for identifying which specific brain regions are degenerating, which can be linked to AD- or FTD-specific neurodegeneration.
Specifically, we aim to 1) Identify specific DNAm marks, unique to brain regions typically degenerated in AD and FTD, including the hippocampus and the lobar regions, using human post-mortem brain samples of AD, FTD and control donors; and 2) Validate the identified biomarkers, by measuring brain-region specific DNAm patterns in cfDNA from peripheral blood of patients and controls.
We expect to find significantly more brain-derived cfDNA in AD and FTD patients compared to controls, aligning with the patterns of neurodegeneration seen in these diseases. This has the potential to revolutionize early diagnosis and tracking of disease progression, especially for AD and FTD.
Our proposed cfDNAm novel biomarker could support timely diagnosis of AD or FTD at early stages, when degeneration has already started but there are no signs and symptoms yet. Also, it has the potential to serve as a prognostic biomarker.

Sign up for updates