Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4

Author:

He Mingyue1ORCID,Liu Zhan1,Lian Tenghong2,Guo Peng2,Zhang Wenjing1,Huang Yue134,Zhang Yanan5,Liu Gaifen13,Zhang Weijiao1,Li Jinghui1,Guan Huiying1,Zhang Weijia1,Luo Dongmei1,Qi Jing1,Yue Hao1,Wang Xiaomin6,Zhang Wei12378ORCID

Affiliation:

1. Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China

2. Center for Cognitive Neurology, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China

3. China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University Beijing China

4. Department of Pharmacology, School of Medical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney New South Wales Australia

5. Department of Blood Transfusion Beijing Tiantan Hospital, Capital Medical University Beijing China

6. Department of Physiology Capital Medical University Beijing China

7. Center of Parkinson's Disease Beijing Institute for Brain Disorders Beijing China

8. Beijing Key Laboratory on Parkinson Disease Beijing China

Abstract

AbstractAimsTo investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4.MethodsTotals of 173 patients with AD were divided into APOE ε4 carrier and non‐carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition.ResultsGlobal cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non‐carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (β, −0.45; 95% CI [−0.96, −0.07]; p < 0.001) and Trail Making Test‐A (time) (β, 0.15; 95% CI [0.01, 0.33]; p < 0.001).ConclusionAPOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4‐associated cognitive impairment.

Publisher

Wiley

Subject

Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology

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