Subtypes Based on Six Apolipoproteins in Non-Demented Elderly Are Associated with Cognitive Decline and Subsequent Tau Accumulation in Cerebrospinal Fluid

Article type: Research Article

Authors: Zou, Shengzhen^a | Zhang, Jie^{b; *} | for Alzheimer’s Disease Neuroimaging Initiative¹ | Chen, Wei^{c; *}

Affiliations: [a] Department of Psychosomatic Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China | [b] Independent Researcher, Hangzhou, China | [c] Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

Correspondence: [*] Correspondence to: Jie Zhang, 25 Xuezheng Road, Xiasha District, Hanghzou, Zhejiang, China. E-mails: jayzhang1014@gmail.com and Wei Chen, Xueyuan West Road 109#, Wenzhou, 325027, Zhejiang Province, PR China. chenwei_008008@163.com.

Note: [1] Data used in preparation of 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 analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Apolipoproteins (APOs) have been implicated in the pathogenesis of Alzheimer’s disease (AD). In the present study, we aimed to investigate if patterns of cerebrospinal fluid (CSF) APOs (APOA-I, APOC-III, APOD, APOE, APOH, and APOJ) levels are associated with changes over time in cognition, memory performance, neuroimaging markers, and AD-related pathologies (CSF Aβ42, t-tau, and p-tau) in non-demented older adults. At baseline, a total of 241 non-demented older adults with CSF APOs data was included in the present analysis. Hierarchical agglomerative cluster analysis including the six CSF APOs was carried out. Among non-demented older adults, we identified two clusters. Compare with the first cluster, the second cluster had higher levels of APOs in CSF. Additionally, the second cluster showed a more benign disease course, including slower cognitive decline and slower p-tau accumulation in CSF. Our data highlight the importance of APOs in the pathogenesis of AD.

Keywords: Alzheimer’s disease, apolipoproteins, cluster analysis, cognitive decline

DOI: 10.3233/JAD-190314

Journal: Journal of Alzheimer's Disease, vol. 72, no. 2, pp. 413-423, 2019