Dataset Information

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.

ABSTRACT: Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ- (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including Aβ40, Aβ42, Aβ42/Aβ40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the Aβ+ group (71.49 ± 25.00 pmol/L) compared with the Aβ- group (56.51 ± 22.14 pmol/L) (P < 0.01). Moreover, Spearman's correlation analysis showed that plasma SOST concentrations were positively correlated with brain Aβ load (ρ = 0.321, P = 0.001). Importantly, plasma SOST combined with Aβ42/Aβ40 ratio significantly increased the area under the curve (AUC) when compared with using Aβ42/Aβ40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.

SUBMITTER: Yuan J

PROVIDER: S-EPMC10477312 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.

Yuan Jun J Pedrini Steve S Thota Rohith R Doecke James J Chatterjee Pratishtha P Sohrabi Hamid R HR Teunissen Charlotte E CE Verberk Inge M W IMW Stoops Erik E Vanderstichele Hugo H Meloni Bruno P BP Mitchell Christopher C Rainey-Smith Stephanie S Goozee Kathryn K Tai Andrew Chi Pang ACP Ashton Nicholas N Zetterberg Henrik H Blennow Kaj K Gao Junjie J Liu Delin D Mastaglia Frank F Inderjeeth Charles C Zheng Minghao M Martins Ralph N RN

npj aging 20230904 1

Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and we ...[more]

PMID: 37666862

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Project description:Importance:The goal of Alzheimer disease (AD) prevention together with advances in understanding the pathophysiology of AD have led to clinical trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data are needed to inform the processes of describing AD biomarkers to cognitively normal adults and assessing their understanding of this knowledge. Objective:To determine the comprehension of an elevated amyloid positron emission tomographic (PET) biomarker result by cognitively unimpaired adults. Design, Setting, and Participants:The Study of Knowledge and Reactions to Amyloid Testing, a substudy of an AD prevention trial, involved 2 semistructured telephone interviews with 80 participants recruited from 9 study sites: 50 received elevated and 30 received not elevated amyloid PET scan results. Interviews were conducted 4 to 12 weeks after result disclosure and again 1 year later. Data presented here were collected from November 5, 2014, through December 10, 2015. The 50 participants included in this study were cognitively normal, aged 65 to 85 years, evenly distributed by gender, and had elevated amyloid PET results. Subsequent reports will examine persons with "not elevated" results and compare the influence of the different results. Main Outcomes and Measures:Participant comprehension of an elevated amyloid result was assessed by analyzing their responses to the following questions: "What was the result of your amyloid PET scan?" (followed by "Can you tell me in your own words what that means?" or "How would you explain it to a friend?"), "Was it the result you expected?" and "Did the result teach you anything or clarify anything for you?" Results:Of the 50 participants aged 65 to 85 years, 49 (98%) were white, 40 (80%) reported a family history of AD, and 30 (60%) had a postgraduate educational level. Most participants (31 [62%]) understood that elevated amyloid conferred an increased but uncertain risk of developing AD. Some desired understanding of the term elevated other than its being a categorical result enabling trial entry eligibility; they wanted information regarding how elevated their amyloid was, how close to the study threshold they were, or percentages, numbers, or a scale to help them make sense of the result. Conclusions and Relevance:Including an explanation of how and why a dimensional biomarker is converted to a categorical classification would enhance future AD biomarker clinical trials and educational materials.

Project description:ObjectiveTo understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults.MethodA total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time.ResultsHigher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant.ConclusionsHigher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.

Dataset Information

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.

Publications

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.

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