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INTRODUCTION: Blood biomarkers accurately identify Alzheimer's disease (AD) pathophysiology and axonal injury. We investigated the influence of food intake on AD‐related biomarkers in cognitively healthy, obese adults at high metabolic risk. METHODS: One‐hundred eleven participants underwent repeated blood sampling during 3 h after a standardized meal (postprandial group, PG). For comparison, blood was sampled from a fasting subgroup over 3 h (fasting group, FG). Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), amyloid‐beta (Aβ) 42/40, phosphorylated tau (p‐tau) 181 and 231, and total‐tau were measured via single molecule array assays. RESULTS: Significant differences were found for NfL, GFAP, Aβ42/40, p‐tau181, and p‐tau231 between FG and PG. The greatest change to baseline occurred for GFAP and p‐tau181 (120 min postprandially, p < 0.0001). CONCLUSION: Our data suggest that AD‐related biomarkers are altered by food intake. Further studies are needed to verify whether blood biomarker sampling should be performed in the fasting state. Highlights: Acute food intake alters plasma biomarkers of Alzheimer's disease in obese, otherwise healthy adults.We also found dynamic fluctuations in plasma biomarkers concentration in the fasting state suggesting physiological diurnal variations.Further investigations are highly needed to verify if biomarker measurements should be performed in the fasting state and at a standardized time of day to improve the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: Blood‐based biomarkers of Alzheimer's disease (AD) may provide an avenue for early identification of individuals at risk for AD dementia, which is a crucial task for implementing upcoming disease‐modifying therapies in clinical practice. Among blood‐based biomarkers, P‐tau217 has shown a particular sensitivity to amyloid pathology and utility for differential diagnosis of AD. However, less is known about the association of P‐tau217 with dementia risk in older primary care patients. Method: To address this question in an extreme phenotype design, we measured plasma P‐tau217 using the validated ALZPath pTau217 assay developed on the Single molecule array (Simoa) technology in 184 patients (median age = 83 years) free of dementia at blood draw who converted to clinically diagnosed dementia of the Alzheimer's type (DAT) during up to eight years of follow‐up. Furthermore, P‐tau217 was measured in 184 age‐ and sex‐matched cognitively normal controls that stayed free of any cognitive impairment during follow‐up. All participants were derived from the primary care‐based AgeCoDe‐cohort. In addition, Aβ42/Aβ40, P‐tau181, NfL, and GFAP were quantified using Simoa technology. Associations between P‐tau217 and conversion to DAT were assessed using conditional logistic regression and compared to associations of conversion to DAT with Aβ42/Aβ40, P‐tau181, NfL, and GFAP. The influence of time to DAT diagnosis on the associations was assessed by generalized additive models. Result: P‐tau217 was strongly associated with conversion to DAT (ORper‐1SD‐increase [95%‐CI] = 10.29 [5.16‐20.41], p = 2.0*10−11, N = 368). This association was present irrespective of whether DAT‐converter showed MCI (ORper‐1SD‐increase [95%‐CI] = 3.49 [1.34‐9.12], p = 1.1*10−2) or no MCI (ORper‐1SD‐increase[95%‐CI] = 16.07[6.54‐39.71], p = 1.3*10−9) at blood draw. No other marker showed a similarly strong association with conversion (second‐best performance: GFAP; ORper‐1SD‐increase [95%‐CI] = 1.36 [1.19‐1.54], p = 2.15*10−2). Patients converting to DAT eight years after blood draw already presented with elevated P‐tau217 levels compared to their matched controls. Other markers (GFAP, P‐tau181) started to show differences in individuals converting to DAT four years after blood draw. Conclusion: P‐tau217 is the most sensitive plasma marker for risk of conversion to DAT in older patients from primary care patients in comparison to plasma P‐tau181, Aβ42/Aβ40, NfL, and GFAP. [ABSTRACT FROM AUTHOR]

Background: Blood biomarker analyses are seen as a great aid to early diagnose and confirm underlying Alzheimer's disease (AD) pathology. Developing evidence suggests that certain confounders need to be considered which may affect the reliability of biomarker results, e.g., chronic kidney disease. However, little is known with respect to potential confounding effects of energy/nutrient intake on these biomarkers. Thus, we aim to study the short‐term effects of oral glucose intake in healthy, obese adults. Method: 111 participants (60±7y, BMI 31±4kg/m2, 47 males) ingested 300ml of a glucose syrup (75g glucose, Accu‐Chek, Roche). Neurofilament light, glial fibrillary acidic protein [GFAP], amyloid‐β 42/40 ratio, phosphorylated tau ([p‐tau] 181 and p‐tau 231) were measured in fasting (0 minutes) and postprandial blood samples collected 15, 30, 45, 60, 120 and 180 minutes after ingestion of the glucose syrup using ultra‐sensitive Single molecule array assays. Additionally, a fasting (control) group (n = 26) was followed over the same time period. Statistical analysis was done using polynomial spline of degree 3 to test for differences in parameter progression over time within and between groups. Result: In both groups, all biomarkers changed significantly over time (glucose group: all p<0.0001, fasting group all p<0.05) compared to baseline (0 minutes). The changes to baseline in GFAP were significantly different after glucose ingestion compared to the fasting state (p<0.0001). The GFAP level decreased in the early postprandial phase (until 60 minutes) and subsequently increased in the late postprandial phase. Conclusion: Our results suggest that plasma biomarkers for AD‐related pathologies are influenced by the individual nutritional status (prolonged fasting, postprandial situation). This should be considered when using AD‐related biomarkers for screening and diagnostic purposes. [ABSTRACT FROM AUTHOR]