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[P4–147]: ISOPRENOIDS PATHWAY, TAU PHOSPHORYLATION AND ALZHEIMER's DISEASE
Author(s) -
Théroux Louise,
Pelleieux Sandra,
Tsantrizos Youla,
Dea Doris,
Poirier Judes
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.2013
Subject(s) - prenylation , geranylgeranyl pyrophosphate , mevalonate pathway , farnesyl pyrophosphate , rhoa , phosphorylation , tau protein , biology , biochemistry , enzyme , gtpase , chemistry , alzheimer's disease , signal transduction , microbiology and biotechnology , medicine , disease , atp synthase , biosynthesis
aphasia (PNFA), 42 corticobasal syndrome (CBS), and 64 progressive supranuclear palsy (PSP) patients. In 73 patients, a definite FTD was diagnosed (underlying pathology: TDP n1⁄450, tau n1⁄423). Results: CSF NfL levels were higher in all patient groups than in controls (p<0.001, sensitivity 79%, specificity 89%). CSF NfL levels were equally elevated in bvFTD, SD, PNFA, CBS, and PSP; FTD-MND patients had higher NfL levels than all other patients. CSF p/t-tau was lower in all patients than controls (p<0.001, sensitivity 73%, specificity 93%), with the lowest values in FTD-MND patients. CSF NfL did not discriminate between underlying TDP and tau pathology (p1⁄40.08). The p/t-tau ratio had a high specificity (81%) and moderate sensitivity (65%) to discriminate FTLDTDP from FTLD-tau patients. In all patients combined, High NfL and low p/t-tau levels were associated with a high CDRSB (rs1⁄40.38, p1⁄40.005 for NfL, rs1⁄4-0.29 for p/t-tau) and with a poor survival (estimated hazard ratio on tertiles 1.7 for NfL and 0.7 for p/t-tau). Conclusions:We confirmed that CSF NfL and the p/t-tau ratio are potential biomarkers for disease severity and prognosis in FTD and are therefore interesting surrogate endpoints in clinical trials. Both biomarkers discriminated FTD from controls, but not the individual subtypes, apart from FTD-MND. Additionally, the p/t-tau ratio was specific to discriminate TDP from tau pathology in vivo.