Plasma Insulin Predicts Early Amyloid-β Pathology Changes in Alzheimer's Disease

Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling.

To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology.

A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages.

In the non-demented group, amyloid-β (Aβ)+ participants (e.g., as reflected by CSF Aβ42) exhibited significantly lower plasma insulin levels compared to non-demented Aβ-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aβ42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aβ42 levels (p < 0.001) across all participants. This association was particularly significant in the Aβ-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aβ42 (p = 0.006), whereas baseline CSF Aβ42 did not show a similar correlation with changes in plasma insulin over time.

These findings suggest an association between plasma insulin and early Aβ pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aβ pathology.