Introduction: Plasma amyloid beta (Aβ)1‐42/Aβ1‐40 ratio, phosphorylated‐tau181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head‐to‐head cross‐sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking.Methods: Plasma Aβ1‐42, Aβ1‐40, p‐tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross‐sectionally across the AD continuum, wherein Aβ‐PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ‐PET–positive participants across the AD continuum (CU Aβ+, n = 39; MCI Aβ+, n = 33; AD Aβ+, n = 46) from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) cohort. Longitudinal plasma biomarker changes were also assessed in MCI (n = 27) and AD (n = 29) participants compared with CU (n = 120) participants. In addition, associations between baseline plasma biomarker levels and prospective cognitive decline and Aβ‐PET load were assessed over a 7 to 10‐year duration.Results: Lower plasma Aβ1‐42/Aβ1‐40 ratio and elevated p‐tau181 and GFAP were observed in CU Aβ+, MCI Aβ+, and AD Aβ+, whereas elevated plasma NfL was observed in MCI Aβ+ and AD Aβ+, compared with CU Aβ− and MCI Aβ−. Among the aforementioned plasma biomarkers, for models with and without AD risk factors (age, sex, and apolipoprotein E (APOE) ε4 carrier status), p‐tau181 performed equivalent to or better than other biomarkers in predicting a brain Aβ−/+ status across the AD continuum. However, for models with and without the AD risk factors, a biomarker panel of Aβ1‐42/Aβ1‐40, p‐tau181, and GFAP performed equivalent to or better than any of the biomarkers alone in predicting brain Aβ−/+ status across the AD continuum. Longitudinally, plasma Aβ1‐42/Aβ1‐40, p‐tau181, and GFAP were altered in MCI compared with CU, and plasma GFAP and NfL were altered in AD compared with CU. In addition, lower plasma Aβ1‐42/Aβ1‐40 and higher p‐tau181, GFAP, and NfL were associated with prospective cognitive decline and lower plasma Aβ1‐42/Aβ1‐40, and higher p‐tau181 and GFAP were associated with increased Aβ‐PET load prospectively.Discussion: These findings suggest that plasma biomarkers are altered cross‐sectionally and longitudinally, along the AD continuum, and are prospectively associated with cognitive decline and brain Aβ‐PET load. In addition, although p‐tau181 performed equivalent to or better than other biomarkers in predicting an Aβ−/+ status across the AD continuum, a panel of biomarkers may have superior Aβ−/+ status predictive capability across the AD continuum.HIGHLIGHTS: Area under the curve (AUC) of p‐tau181 ≥ AUC of Aβ42/40, GFAP, NfL in predicting PET Aβ−/+ status (Aβ−/+). AUC of Aβ42/40+p‐tau181+GFAP panel ≥ AUC of Aβ42/40/p‐tau181/GFAP/NfL for Aβ−/+. Longitudinally, Aβ42/40, p‐tau181, and GFAP were altered in MCI versus CU. Longitudinally, GFAP and NfL were altered in AD versus CU. Aβ42/40, p‐tau181, GFAP, and NfL are associated with prospective cognitive decline. Aβ42/40, p‐tau181, and GFAP are associated with increased PET Aβ load prospectively.

Dietary supplementation with curcumin has been previously reported to have beneficial effects in people with insulin resistance, type 2 diabetes (T2D) and Alzheimer’s disease (AD). This study investigated the effects of dietary supplementation with curcumin on key peptides implicated in insulin resistance in individuals with high risk of developing T2D. Plasma samples from participants recruited for a randomised controlled trial with curcumin (180 mg/day) for 12 weeks were analysed for circulating glycogen synthase kinase-3 β (GSK-3β) and islet amyloid polypeptide (IAPP). Outcome measures were determined using ELISA kits. The homeostasis model for assessment of insulin resistance (HOMA-IR) was measured as parameters of glycaemic control. Curcumin supplementation significantly reduced circulating GSK-3β (−2.4 ± 0.4 ng/mL vs. −0.3 ± 0.6, p = 0.0068) and IAPP (−2.0 ± 0.7 ng/mL vs. 0.4 ± 0.6, p = 0.0163) levels compared with the placebo group. Curcumin supplementation significantly reduced insulin resistance (−0.3 ± 0.1 vs. 0.01 ± 0.05, p = 0.0142) compared with placebo group. Dietary supplementation with curcumin reduced circulating levels of IAPP and GSK-3β, thus suggesting a novel mechanism through which curcumin could potentially be used for alleviating insulin resistance related markers for reducing the risk of T2D and AD.

Lowering insulin resistance and dyslipidaemia may not only enhance glycaemic control but also preserve the β-cell function, reducing the overall risk of developing type 2 diabetes (T2D). The current study was aimed to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) supplementation on glycaemic control and blood lipid levels in individuals at high risk of developing T2D. This was a 2 × 2 factorial, randomised, double-blinded, placebo-controlled study. Participants were allocated to either double placebo (PL) or curcumin plus placebo matching for LCn-3PUFA (CC), or LCn-3PUFA plus placebo matching for curcumin (FO), or curcumin plus LCn-3PUFA (CC-FO) for twelve weeks. Primary outcome of the trial was glycaemic indices (HbA1C, fasting glucose and insulin). Insulin resistance and sensitivity is measured using homeostatic model assessment model. A total of sixty-four participants (PL, n = 16; CC, n = 15; FO, n = 17, CC-FO, n = 16) were included in the final analysis. Post-intervention, HbA1c and fasting glucose remained unchanged across all the groups. Insulin sensitivity was significantly improved in the CC supplemented group (32.7 ± 10.3%) compared to PL (P = 0.009). FO and CC-FO tended to improve insulin sensitivity by 14.6 ± 8.5% and 8.8 ± 7.7% respectively, but the difference did not reach significance. Triglyceride levels were further increased in the PL (26.9 ± 7.4%), however, CC and CC-FO supplementation reduced the triglycerides, FO resulted in the greatest reduction in triglycerides (− 16.4 ± 4.5%, P < 0.001). Reduction in insulin resistance and triglycerides by curcumin and LCn-3PUFA appears to be attractive strategies for lowering the risk of developing T2D. However, this study failed to demonstrate complimentary benefits of curcumin and LCn-3PUFA on glycaemic control. ACTRN12615000559516 .

The anti-inflammatory effects of curcumin are well documented. However, the bioavailability of curcumin is a major barrier to its biological efficacy. Low-dose combination of complimentary bioactives appears to be an attractive strategy for limiting barriers to efficacy of bioactive compounds. In this study, the anti-inflammatory potential of curcumin in combination with chlorogenic acid (CGA), was investigated using human THP-1 macrophages stimulated with lipopolysaccharide (LPS). Curcumin alone suppressed TNF-α production in a dose-dependent manner with a decrease in cell viability at higher doses. Although treatment with CGA alone had no effect on TNF-α production, it however enhanced cell viability and co-administration with curcumin at a 1:1 ratio caused a synergistic reduction in TNF-α production with no impact on cell viability. Furthermore, an qRT-PCR analysis of NF-κB pathway components and inflammatory biomarkers indicated that CGA alone was not effective in reducing the mRNA expression of any of the tested inflammatory marker genes, except TLR-4. However, co-administration of CGA with curcumin, potentiated the anti-inflammatory effects of curcumin. Curcumin and CGA together reduced the mRNA expression of pro-inflammatory cytokines [TNF-α (~88%) and IL-6 (~99%)], and COX-2 (~92%), possibly by suppression of NF-κB (~78%), IκB-β-kinase (~60%) and TLR-4 receptor (~72%) at the mRNA level. Overall, co-administration with CGA improved the inflammation-lowering effects of curcumin in THP-1 cells.

Lower incidence of cardiovascular disease (CVD) in the Greenland Inuit, Northern Canada and Japan has been attributed to their consumption of seafood rich in long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA).

Background: Evidence has suggested that omega-3 (n–3) polyunsaturated fatty acids (PUFAs) improve obesity-induced insulin resistance (IR); however, r