TY  - JOUR
AU  - Murthy, Megha
AU  - Rizzu, Patrizia
AU  - Heutink, Peter
AU  - Mill, Jonathan
AU  - Lashley, Tammaryn
AU  - Bettencourt, Conceição
TI  - Epigenetic Age Acceleration in Frontotemporal Lobar Degeneration: A Comprehensive Analysis in the Blood and Brain.
JO  - Cells
VL  - 12
IS  - 14
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2023-00758
SP  - 1922
PY  - 2023
AB  - Frontotemporal lobar degeneration (FTLD) includes a heterogeneous group of disorders pathologically characterized by the degeneration of the frontal and temporal lobes. In addition to major genetic contributors of FTLD such as mutations in MAPT, GRN, and C9orf72, recent work has identified several epigenetic modifications including significant differential DNA methylation in DLX1, and OTUD4 loci. As aging remains one of the major risk factors for FTLD, we investigated the presence of accelerated epigenetic aging in FTLD compared to controls. We calculated epigenetic age in both peripheral blood and brain tissues of multiple FTLD subtypes using several DNA methylation clocks, i.e., DNAmClockMulti, DNAmClockHannum, DNAmClockCortical, GrimAge, and PhenoAge, and determined age acceleration and its association with different cellular proportions and clinical traits. Significant epigenetic age acceleration was observed in the peripheral blood of both frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) patients compared to controls with DNAmClockHannum, even after accounting for confounding factors. A similar trend was observed with both DNAmClockMulti and DNAmClockCortical in post-mortem frontal cortex tissue of PSP patients and in FTLD cases harboring GRN mutations. Our findings support that increased epigenetic age acceleration in the peripheral blood could be an indicator for PSP and to a smaller extent, FTD.
KW  - Humans
KW  - Frontotemporal Dementia
KW  - Frontotemporal Lobar Degeneration: genetics
KW  - Brain
KW  - Supranuclear Palsy, Progressive: genetics
KW  - Mutation: genetics
KW  - Ubiquitin-Specific Proteases
KW  - DNA methylation aging (Other)
KW  - epigenetic clock (Other)
KW  - frontotemporal dementia (Other)
KW  - frontotemporal lobar degeneration (Other)
KW  - progressive supranuclear palsy (Other)
KW  - OTUD4 protein, human (NLM Chemicals)
KW  - Ubiquitin-Specific Proteases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37508584
C2  - pmc:PMC10378390
DO  - DOI:10.3390/cells12141922
UR  - https://pub.dzne.de/record/259686
ER  -