Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease

• Published in: Alzheimer's research & therapy Vol. 7; no. 1; p. 74
• Main Authors: Hellwig, Konstantin, Kvartsberg, Hlin, Portelius, Erik, Andreasson, Ulf, Oberstein, Timo Jan, Lewczuk, Piotr, Blennow, Kaj, Kornhuber, Johannes, Maler, Juan Manuel, Zetterberg, Henrik, Spitzer, Philipp
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.12.2015; BioMed Central
• Subjects: Adipokines - cerebrospinal fluid; Adipokines - metabolism; Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; amyloid-beta; Analysis; association workgroups; Biological markers; biomarkers; Biomarkers - cerebrospinal fluid; cerebrospinal-fluid; Chitinase-3-Like Protein 1; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; dementia; Development and progression; Diagnosis; diagnostic guidelines; disease; Disease Progression; Female; Humans; Lectins - cerebrospinal fluid; Lectins - metabolism; Male; Middle Aged; mild cognitive impairment; national institute; neurodegenerative; neurogranin; Neurogranin - cerebrospinal fluid; Neurogranin - metabolism; Neurologi; Neurology; Neurosciences; Neurosciences & Neurology; Neurovetenskaper; protein; tau Proteins - cerebrospinal fluid; United States
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-015-0161-y

Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer's disease (AD). Neurogranin and YKL-40 in cerebrospinal fluid (CSF) are newly discovered markers indicating synaptic damage and microglial activation, respectively. CSF samples from 95 individuals including 39 patients with AD dementia (AD-D), 13 with mild cognitive impairment (MCI) due to AD (MCI-AD), 29 with MCI not due to AD (MCI-o) and 14 patients with non-AD dementias (non-AD-D) were analyzed for neurogranin and YKL-40. Patients with dementia or MCI due to AD showed elevated levels of CSF neurogranin (p < 0.001 for AD-D and p < 0.05 for MCI-AD) and YKL-40 (p < 0.05 for AD-D and p = 0.15 for MCI-AD) compared to mildly cognitively impaired subjects not diagnosed with AD. CSF levels of neurogranin and YKL-40 did not differ between MCI not due to AD and non-AD dementias. In AD subjects no correlation between YKL-40 and neurogranin was found. The CSF neurogranin levels correlated moderately with tau and p-tau but not with Aβ42 or the MMSE in AD samples. No relevant associations between YKL-40 and MMSE or the core AD biomarkers, Aβ42, t-tau and p-tau were found in AD subjects. Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core AD biomarkers, reflecting additional pathological changes in the course of AD.