Lumbar puncture increases Alzheimer's disease biomarker levels in cerebrospinal fluid of rhesus monkeys

Jianglei Xu; Hao Li; Yingzhou Hu; Shihao Wu; Liping Wu; Xiaoguang Lei; Longbao Lv; Yi Lu; Jing Wu; Juanjuan Li; Bingyin Shi; Jiali Li; Christoph W Turck; Wenchao Wang; Xintian Hu

doi:10.1016/j.isci.2024.109436

Lumbar puncture increases Alzheimer's disease biomarker levels in cerebrospinal fluid of rhesus monkeys

iScience. 2024 Mar 6;27(4):109436. doi: 10.1016/j.isci.2024.109436. eCollection 2024 Apr 19.

Authors

Jianglei Xu^{1

2

3}, Hao Li^{1

2}, Yingzhou Hu^{1

2}, Shihao Wu⁴, Liping Wu⁵, Xiaoguang Lei⁶, Longbao Lv^{1

2

3}, Yi Lu⁷, Jing Wu^{1

2}, Juanjuan Li⁸, Bingyin Shi⁵, Jiali Li⁹, Christoph W Turck^{1

2

10}, Wenchao Wang^{1

2}, Xintian Hu^{1

2}

Affiliations

¹ National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
² Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
³ Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming 650204, China.
⁴ School of Medicine, Yunnan University, Kunming, Yunnan 650000, China.
⁵ Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
⁶ First Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
⁷ Department of Medical Imaging, First Affiliated Hospital of Kunming Medical University, Kunming 650000, China.
⁸ Department of Ophthalmology, Yan'an Hospital Affiliated to Kunming Medical University, Kunming 650051, China.
⁹ Department of Neurology, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.
¹⁰ Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, 80804 Munich, Germany.

Abstract

Cerebrospinal fluid (CSF) samples are commonly collected via lumbar puncture (LP) in both clinical and research settings for measurement of biomarkers of Alzheimer's disease (AD). To determine the effects of LP on CSF AD biomarkers, we collected CSF samples at seven different time points after an LP in rhesus monkeys. We find that amyloid-beta (Aβ) and Tau levels increased significantly on day 1, peaked on day 3, and returned to baseline on day 10 after LP. The NFL levels increased significantly on day 5, peaked on day 10, and returned to baseline after day 30. The increased AD biomarker levels were mainly due to CSF outflow and deep intrathecal invasion during LP. Therefore, if LPs are repeated within a short period of time, prior LP can affect Aβ and Tau levels within 10 days and NFL levels within 30 days, which may lead to clinical misdiagnosis or incorrect scientific conclusions.

Keywords: Molecular medicine; Molecular neuroscience.