Physiological functions of tau remain ill defined. In the present study, Marciniak et al. uncover a novel function of tau in its ability to regulate brain insulin signaling and discuss the pathophysiological implications of these findings for Alzheimer’s disease and tauopathies.

ing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents. -Bokor, S., J. Dumont, A. Spinneker, M. GonzalezGross, E. Nova, K. Widhalm, G. Moschonis, P. Long-chain PUFA (LCPUFA) have a key role in maintaining biological functions in humans; they are components of the cell membrane, serve as substrates for the synthesis of infl ammatory eicosanoids (leukotrienes and prostaglandins), act as signaling molecules, and regulate gene expression ( 1, 2 ). The FA composition of plasma and Abstract Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/ C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1 . In contrast, only the rs968567 minor allele was associated with higher D6D activity ( P = 1.5E-6). This fi nding agrees with an earlier in vitro study show- 28 April 2010. Published, JLR Papers in Press, April 28, 2010 DOI 10.1194 Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios Abbreviations: BMI, body mass index; D5D, delta-5 desaturase; D6D, delta-6 desaturase; LCPUFA, long-chain PUFA; SNP, single nucleotide polymorphism; TG, triglyceride. The HELENA Study receives funding from the European Union's Sixth RTD Framework Program (contract FOOD-CT-2005-007034), the Spanish Ministry of Education (EX-2007-1124, AGL2007-29784-E/ALI; AP-2005-3827), Universidad Politécnica de Madrid (CH/018/2008), and Cognis GmbH (Germany). The writing group takes sole responsibility for the content of this article and the European Union is not liable for any use that may be made of the information contained herein. This work was supported by the Conseil Régional du Nord-Pas de Calais, ERDF (European Regional Development Fund) in the frame of the CPER Cardio-diabete (convention 09220016). Manuscript received 17 February 2010 and in revised form