Association of cerebrospinal fluid Neurogranin with Alzheimer’s disease
Cerebrospinal fluid (CSF) Neurogranin has recently been proposed as a potential biomarker for cognitive decline and brain injury in Alzheimer’s disease (AD). To test whether CSF Neurogranin levels are increased in AD and its association with cognitive decline, we examined 99 cognitively normal (CN) subjects, 171 patients with mild cognitive impairment (MCI), and 81 patients with AD in the cross-sectional study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The results showed that CSF Neurogranin was increased in both AD and MCI compared with controls. CSF Neurogranin was particularly high in patients with MCI and AD dementia with Aβ pathologic features. Neurogranin levels were significantly higher in females compared to males with MCI. Levels of Neurogranin between the males and females with AD and CN did not differ. Neurogranin levels were significantly higher in APOE ε4 carriers compared to APOE ε4 non-carriers with MCI. Levels of Neurogranin between the APOE ε4 carriers and APOE ε4 non-carriers with AD and CN did not differ. Elevated CSF Neurogranin levels were positively correlated with levels of total tau and P-tau in AD. The results indicated that CSF Neurogranin was increased at the prodromal stage of AD and might reflect synaptic injury as cognitive decline in AD.
KeywordsAlzheimer’s disease Neurogranin Cerebrospinal fluid Mild cognitive impairment
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the study involving human participant were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all participants or authorized representative.
- 22.Baudier J, Deloulme JC, Van Dorsselaer A et al (1991) Purification and characterization of a brain-specific protein kinase C substrate, Neurogranin (p17). Identification of a consensus amino acid sequence between Neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain. J Biol Chem 266:229–237PubMedGoogle Scholar