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

Article type: Research Article

Authors: Chen, Yu-Han^{a; 1} | Wang, Zhi-Bo^{b; 1} | Liu, Xi-Peng^c | Mao, Zhi-Qi^{d; *} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] The First Clinical Medical School, Hebei North University, Zhangjiakou, China | [b] Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China | [c] Department of Neurosurgery, The First Affiliated Hospital of Hebei North University, Hebei, Zhangjiakou, China | [d] Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China

Correspondence: [*] Correspondence to: Dr. Zhi-Qi Mao, MD, PhD, Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, Haidian District 100853, People’s Republic of China. Tel.: +86 18910155994; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-ontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background: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. Objective:To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: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. Results: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. Conclusions: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.

Keywords: Alzheimer’s disease, amyloid, diabetes, plasma insulin, pTau

DOI: 10.3233/JAD-240289

Journal: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 321-332, 2024