Isoprenoids and tau pathology in sporadic Alzheimer's disease.

TitleIsoprenoids and tau pathology in sporadic Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsPelleieux S, Picard C, Lamarre-Théroux L, Dea D, Leduc V, Tsantrizos YS, Poirier J
JournalNeurobiol Aging
Volume65
Pagination132-139
Date Published2018 May
ISSN1558-1497
Abstract

The mevalonate pathway has been described to play a key role in Alzheimer's disease (AD) physiopathology. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are nonsterol isoprenoids derived from mevalonate, which serve as precursors to numerous human metabolites. They facilitate protein prenylation; hFPP and hGGPP synthases act as gateway enzymes to the prenylation of the small guanosine triphosphate (GTP)ase proteins such as RhoA and cdc42 that have been shown to facilitate phospho-tau (p-Tau, i.e., protein tau phosphorylated) production in the brain. In this study, a significant positive correlation was observed between the synthases mRNA prevalence and disease status (FPPS, p < 0.001, n = 123; GGPPS, p < 0.001, n = 122). The levels of mRNA for hFPPS and hGGPPS were found to significantly correlate with the amount of p-Tau protein levels (p < 0.05, n = 34) and neurofibrillary tangle density (p < 0.05, n = 39) in the frontal cortex. Interestingly, high levels of hFPPS and hGGPPS mRNA prevalence are associated with earlier age of onset in AD (p < 0.05, n = 58). Together, these results suggest that accumulation of p-Tau in the AD brain is related, at least in part, to increased levels of neuronal isoprenoids.

DOI10.1016/j.neurobiolaging.2018.01.012
Alternate JournalNeurobiol. Aging
PubMed ID29476987

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