Abstract
It was unclear whether sex hormone-binding globulin (SHBG) was a circulating biomarker of Alzheimer’s disease (AD). We tested the cross-sectional relationships between plasma SHBG and cerebrospinal fluid (CSF) AD biomarkers in 707 non-demented adults. Next, the influences of plasma SHBG on dynamic changes of CSF Aβ42, hippocampus volume, brain metabolism, and cognition were explored in 448 non-demented adults from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Finally, the predictive and diagnostic values of plasma SHBG in AD were explored. A positive correlation was found between SHBG levels in plasma and CSF. Individuals with higher plasma SHBG levels had lower CSF Aβ42 (p < 0.005), after adjusting for age, gender, education, APOE4 allele, and cognitive scores. Though no significant difference of plasma SHBG was observed between mild AD dementia and healthy normal, plasma SHBG could contribute to accelerated rates of CSF Aβ42 decrease (p < 0.0005), decline in brain metabolism (p < 0.05), and hippocampus atrophy (p < 0.01), cognitive decline (p < 0.01), as well as higher risk of AD dementia (p < 0.05). These findings indicated plasma SHBG could be a prodromal biomarker to predict disease progression in AD.
Highlights
Sex hormone-binding globulin (SHBG) in plasma has been found to be significantly elevated in subjects with Alzheimer’s disease (AD)
Sex hormone-binding globulin (SHBG) in plasma has been found to be significantly elevated in subjects with AD than their matched controls[1], suggesting plasma SHBG might be involved in occurrence of AD via unclear mechanisms
We aimed to investigate whether plasma SHBG could predict neurodegeneration and clinical progression in prodromal AD: 1) we first tested whether plasma SHBG was associated with cerebrospinal fluid (CSF) AD biomarkers; 2) we explored the values of plasma SHBG in predicting longitudinal changes of CSF AD biomarkers, imaging, and cognition; 3) we examined whether plasma SHBG was associated with AD risk
Summary
Sex hormone-binding globulin (SHBG) in plasma has been found to be significantly elevated in subjects with AD. We aimed to investigate whether plasma SHBG was associated with AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. It was hypothesized that the breach of equilibrium between the bound and free state might disturb the normal neuroprotective functioning of sex steroids[3 4] Till it was still controversial for the relationship between plasma SHBG and AD risk. Most researchers focused on their cross-sectional relationships and the conclusions were disputable possibly due to varying sources of biases, such as small sample size and case ascertainment[1 5−8] Their longitudinal associations were inconsistently reported[5 9 10]. We aimed to investigate whether plasma SHBG could predict neurodegeneration and clinical progression in prodromal AD: 1) we first tested whether plasma SHBG was associated with CSF AD biomarkers; 2) we explored the values of plasma SHBG in predicting longitudinal changes of CSF AD biomarkers, imaging, and cognition; 3) we examined whether plasma SHBG was associated with AD risk
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