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000259686 1001_ $$aMurthy, Megha$$b0
000259686 245__ $$aEpigenetic Age Acceleration in Frontotemporal Lobar Degeneration: A Comprehensive Analysis in the Blood and Brain.
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000259686 520__ $$aFrontotemporal 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.
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000259686 650_7 $$2Other$$aDNA methylation aging
000259686 650_7 $$2Other$$aepigenetic clock
000259686 650_7 $$2Other$$afrontotemporal dementia
000259686 650_7 $$2Other$$afrontotemporal lobar degeneration
000259686 650_7 $$2Other$$aprogressive supranuclear palsy
000259686 650_7 $$0EC 3.4.19.12$$2NLM Chemicals$$aOTUD4 protein, human
000259686 650_7 $$0EC 3.4.19.12$$2NLM Chemicals$$aUbiquitin-Specific Proteases
000259686 650_2 $$2MeSH$$aHumans
000259686 650_2 $$2MeSH$$aFrontotemporal Dementia
000259686 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: genetics
000259686 650_2 $$2MeSH$$aBrain
000259686 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: genetics
000259686 650_2 $$2MeSH$$aMutation: genetics
000259686 650_2 $$2MeSH$$aUbiquitin-Specific Proteases
000259686 7001_ $$0P:(DE-2719)2810718$$aRizzu, Patrizia$$b1$$udzne
000259686 7001_ $$0P:(DE-2719)2810728$$aHeutink, Peter$$b2$$udzne
000259686 7001_ $$aMill, Jonathan$$b3
000259686 7001_ $$00000-0001-7389-0348$$aLashley, Tammaryn$$b4
000259686 7001_ $$00000-0001-9090-7690$$aBettencourt, Conceição$$b5
000259686 770__ $$aAdvances in the Understanding of Frontotemporal Dementia
000259686 773__ $$0PERI:(DE-600)2661518-6$$a10.3390/cells12141922$$gVol. 12, no. 14, p. 1922 -$$n14$$p1922$$tCells$$v12$$x2073-4409$$y2023
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