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Plasma amyloid ? 42/40 ratios as biomarkers for amyloid ? cerebral deposition in cognitively normal individuals.

ABSTRACT: Plasma amyloid ? (A?) peptides have been previously studied as candidate biomarkers to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease.Free and total A?42/40 plasma ratios (FP42/40 and TP42/40, respectively) were determined using ABtest assays in cognitively normal subjects from the Australian Imaging, Biomarker and Lifestyle Flagship Study. This population was followed-up for 72 months and their cortical A? burden was assessed with positron emission tomography.Cross-sectional and longitudinal analyses showed an inverse association of A?42/40 plasma ratios and cortical A? burden. Optimized as a screening tool, TP42/40 reached 81% positive predictive value of high cortical A? burden, which represents 110% increase over the population prevalence of cortical A? positivity.These findings support the use of plasma A?42/40 ratios as surrogate biomarkers of cortical A? deposition and enrichment tools, reducing the number of subjects submitted to invasive tests and, consequently, recruitment costs in clinical trials targeting cognitively normal individuals.

SUBMITTER: Fandos N

PROVIDER: S-EPMC5602863 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals.

Fandos Noelia N Pérez-Grijalba Virginia V Pesini Pedro P Olmos Salvador S Bossa Matías M Villemagne Victor L VL Doecke James J Fowler Christopher C Masters Colin L CL Sarasa Manuel M

Alzheimer's & dementia (Amsterdam, Netherlands) 20170912

<h4>Introduction</h4>Plasma amyloid β (Aβ) peptides have been previously studied as candidate biomarkers to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease.<h4>Methods</h4>Free and total Aβ42/40 plasma ratios (FP42/40 and TP42/40, respectively) were determined using ABtest assays in cognitively normal subjects from the Australian Imaging, Biomarker and Lifestyle Flagship Study. This population was followed-up for 72 months and their cortical Aβ bur ...[more]

PMID: 28948206

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Project description:Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD.Cross-sectional study.Manhattan (broader area).Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-?, A?) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined.Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers.None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ?-3 and ?-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter.Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on A? and associated neuronal impairment.

Project description:ObjectivesRecent studies regarding the relationships between plasma amyloid-β (Aβ) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ levels in a large-sample cognitively normal population.MethodsThis population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aβ levels (Aβ40, Aβ42, and Aβ42 / 40).ResultsParticipants with moderate Aβ40 levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aβ40 [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45-0.81, p < 0.001] or high Aβ40 (OR: 0.65, 95% CI: 0.49-0.87, p = 0.004) levels. The association between Aβ40 and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and > 65 years) and Aβ40 (p for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aβ40 and cognitive decline (OR: 1.02, 95% CI: 1.00-1.04, p = 0.027). For participants ≤ 65 years old, the lower Aβ40 and higher Aβ40 groups had a lower risk of cognitive decline than the medium Aβ40 group (OR: 0.69, 95% CI: 0.50-0.94, p = 0.02; OR: 0.63, 95% CI: 0.45-0.86, p = 0.004). None of relationship between plasma Aβ42, Aβ42 / 40 and cognitive decline was found during a 2-year follow-up.ConclusionThe relationship between plasma Aβ40 and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.

Dataset Information

Plasma amyloid ? 42/40 ratios as biomarkers for amyloid ? cerebral deposition in cognitively normal individuals.

Publications

Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals.

Similar Datasets

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