Aβ misfolding in blood plasma is inversely associated with body mass index even in middle adulthood

Abstract

Background To understand the potential for early intervention and prevention measures in Alzheimer’s disease, the association between risk factors and early pathological change needs to be assessed. Hence, the aim of this study was to determine whether risk factors of Alzheimer’s clinical syndrome (clinical AD), such as body mass index (BMI), are associated with Aβ misfolding in blood, a strong risk marker for AD among older adults. Methods Information on risk factors and blood samples were collected at baseline in the ESTHER study, a population-based cohort study of older adults (age 50–75 years) in Germany. Aβ misfolding in blood plasma was analyzed using an immuno-infrared-sensor in a total of 872 participants in a nested case-control design among incident dementia cases and matched controls. Associations between risk factors and Aβ misfolding were assessed by multiple logistic regression. For comparison, the association between the risk factors and AD incidence during 17 years of follow-up was investigated in parallel among 5987 cohort participants. Results An inverse association with Aβ misfolding was seen for BMI at age 50 based on reported weight history (aOR 0.64, 95% CI 0.43–0.96, p = 0.03). Similar but not statistically significant associations were seen for BMI at baseline (i.e., mean age 68) and at age 40. No statistically significant associations with Aβ misfolding were found for other risk factors, such as diabetes, smoking, and physical activity. On the other hand, low physical activity was associated with a significantly reduced risk of developing clinical AD compared to physical inactivity. Conclusions Our results support that AD pathology may be detectable and associated with reduced weight even in middle adulthood, many years before clinical diagnosis of AD. Physical activity might reduce the risk of onset of AD symptoms.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid‐beta levels

“…Therefore, BMI may be a common contributing factor towards OSA and neurodegenerative changes. Though some studies reported an association of lower BMI with increased amyloid burden, however, the weight loss might have been due to disturbed eating behaviour in Alzheimer's disease (Hsu et al, 2016;Möllers et al, 2021). Multivariate logistic regression analysis revealed that Total tau (pg ml -1 ) 168.5 (85.9) 10.9 (101.5) 0.0000 P-tau (pg ml -1 ) 8.1 (10.4) 10.2 (13.4) 0.6287…”

Independent effect of body mass index variation on amyloid-β positivity

“…Recently, being underweight or obese in mid-life was found to be associated with an increased risk of Aβ deposition (Gottesman et al, 2017;Lee et al, 2020;Möllers et al, 2021), and individuals who are underweight in later life were also at an increased risk of Aβ deposition (Vidoni et al, 2011;Ewers et al, 2012;Hsu et al, 2016;Thirunavu et al, 2019). However, since previous studies investigated the association of BMI with Aβ deposition at a single time point, these studies could not evaluate the effects of BMI variability on Aβ deposition.…”