BACE1 and Other Alzheimer’s-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer’s Disease Patients from Cognitively-Impaired Neurosyphilis Patients

Article type: Research Article

Authors: Zhang, Min^a | Zhong, Xiaomei^b | Shi, Haishan^a | Vanmechelen, Eugeen^e | De Vos, Ann^e | Liu, Sen^f | Chen, Ben^b | Mai, Naikeng^a | Peng, Qi^b | Chen, Xinru^a | Wu, Zhangying^b | Hou, Le^a | Zhou, Huarong^a | Ouyang, Cong^b | Zhang, Weiru^b | Liang, Wanyuan^b | Dai, Chunying^b | Ning, Yuping^{a; c; d; *}

Affiliations: [a] Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China | [b] Department of Geriatric Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China | [c] The first School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China | [d] Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China | [e] ADx NeuroSciences NV, Ghent, Belgium | [f] Beijing Seven Dimension Neuroscience Research Center, Beijing, China

Correspondence: [*] Correspondence to: Yuping Ning, Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, China. Tel.: +8620 8126 8720; Fax: +8620 8189 1391; E-mail: [email protected].

Abstract: Background:Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer’s disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. Objective:To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Methods:Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1–40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Results:Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. Conclusion:GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

Keywords: Alzheimer’s disease, BACE1, general paresis of insane, neurogranin, neurosyphilis

DOI: 10.3233/JAD-200362

Journal: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 313-322, 2020