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J Alzheimers Dis. 2016 Jul 6;53(4):1523-38. doi: 10.3233/JAD-160227.

The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease.

Author information

1
ADx NeuroSciences NV, Technologiepark Zwijnaarde 4, 9052 Gent, Belgium.
2
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
3
StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
4
Department of Neuropathology, Pitié-Salpêtrière Hospital, Paris, France.
5
Developmental and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
6
Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium.
7
Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
8
Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

Abstract

BACKGROUND:

In diagnosing Alzheimer's disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers.

OBJECTIVE:

We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios.

METHODS:

Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychological (MMSE) examinations for at least one year.

RESULTS:

The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio.

CONCLUSION:

This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline.

KEYWORDS:

Alzheimer’s disease; BACE1 protein; ELISA; biomarkers; cerebrospinal fluid; mild cognitive impairment; neurogranin; prognostic; ratio

PMID:
27392859
PMCID:
PMC4981899
DOI:
10.3233/JAD-160227
[Indexed for MEDLINE]
Free PMC Article

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