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The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease

Cerebrospinal fluid (CSF) measurements of neurogranin (Ng) have emerged as a promising biomarker for cognitive decline in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The apolipoprotein E ε4 (APOE ε4) allele is by far the most consistent genetic risk factor for AD. However, it is no...

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Autores principales: Fan, Yulan, Gao, Ying, Therriault, Joseph, Luo, Jing, Ba, Maowen, Zhang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110906/
https://www.ncbi.nlm.nih.gov/pubmed/33986657
http://dx.doi.org/10.3389/fnagi.2021.667899
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author Fan, Yulan
Gao, Ying
Therriault, Joseph
Luo, Jing
Ba, Maowen
Zhang, Hua
author_facet Fan, Yulan
Gao, Ying
Therriault, Joseph
Luo, Jing
Ba, Maowen
Zhang, Hua
author_sort Fan, Yulan
collection PubMed
description Cerebrospinal fluid (CSF) measurements of neurogranin (Ng) have emerged as a promising biomarker for cognitive decline in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The apolipoprotein E ε4 (APOE ε4) allele is by far the most consistent genetic risk factor for AD. However, it is not known whether the pathophysiological roles of Ng in MCI or AD are related to APOEε4. We stratified 250 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN) ε4 negative (CN ε4−), CN ε4 positive (CN ε4+), MCI ε4 negative (MCI ε4−), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4−), and AD ε4 positive (AD ε4+). CSF Ng levels were significantly increased in APOE ε4 carriers compared to APOE ε4 non-carriers with MCI. In addition, CSF Ng identified MCI ε4+ versus CN ε4−, but not MCI ε4− versus CN ε4−. Similarly, CSF Ng negatively correlated with Mini-Mental State Examination (MMSE) scores at baseline in the MCI ε4+ group. Our findings support the use of CSF Ng as a biomarker of synaptic pathology for AD. We propose that the roles of CSF Ng in the pathophysiology of MCI may be related to APOE ε4.
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spelling pubmed-81109062021-05-12 The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease Fan, Yulan Gao, Ying Therriault, Joseph Luo, Jing Ba, Maowen Zhang, Hua Front Aging Neurosci Neuroscience Cerebrospinal fluid (CSF) measurements of neurogranin (Ng) have emerged as a promising biomarker for cognitive decline in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The apolipoprotein E ε4 (APOE ε4) allele is by far the most consistent genetic risk factor for AD. However, it is not known whether the pathophysiological roles of Ng in MCI or AD are related to APOEε4. We stratified 250 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN) ε4 negative (CN ε4−), CN ε4 positive (CN ε4+), MCI ε4 negative (MCI ε4−), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4−), and AD ε4 positive (AD ε4+). CSF Ng levels were significantly increased in APOE ε4 carriers compared to APOE ε4 non-carriers with MCI. In addition, CSF Ng identified MCI ε4+ versus CN ε4−, but not MCI ε4− versus CN ε4−. Similarly, CSF Ng negatively correlated with Mini-Mental State Examination (MMSE) scores at baseline in the MCI ε4+ group. Our findings support the use of CSF Ng as a biomarker of synaptic pathology for AD. We propose that the roles of CSF Ng in the pathophysiology of MCI may be related to APOE ε4. Frontiers Media S.A. 2021-04-27 /pmc/articles/PMC8110906/ /pubmed/33986657 http://dx.doi.org/10.3389/fnagi.2021.667899 Text en Copyright © 2021 Fan, Gao, Therriault, Luo, Ba and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Fan, Yulan
Gao, Ying
Therriault, Joseph
Luo, Jing
Ba, Maowen
Zhang, Hua
The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title_full The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title_fullStr The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title_full_unstemmed The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title_short The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease
title_sort effects of csf neurogranin and apoe ε4 on cognition and neuropathology in mild cognitive impairment and alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110906/
https://www.ncbi.nlm.nih.gov/pubmed/33986657
http://dx.doi.org/10.3389/fnagi.2021.667899
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