title: Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer's disease.
abstract: Synaptic pathology occurs early in Alzheimer's disease (AD) development, and cerebrospinal fluid biomarkers for synaptic damage may be altered early in the disease process. In the present study we examined cerebrospinal fluid levels of the postsynaptic protein neurogranin in patients with mild cognitive impairment (MCI) or AD and controls. The low neurogranin level in cerebrospinal fluid required enrichment by immunoprecipitation prior to mass spectrometric identification and semi-quantitative immunoblot analysis. Relative quantification revealed a significant increase of neurogranin in the AD group compared with controls, while the MCI group was not statistically different from either controls or the AD group. The concentrations of the AD biomarkers T-tau, P-tau(181) and Aβ(42) were significantly changed in the control and MCI groups compared with the AD group, but no significant differences were found between the MCI group and controls for the three biomarkers. Nevertheless, a trend towards increasing levels of neurogranin, T-tau and P-tau(181) was found in cerebrospinal fluid from MCI patients compared with controls. The elevated neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. annika.thorsell@neuro.gu.se
authors.forename: Annika
authors.initials: A
authors.lastname: Thorsell
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.forename: Eva
authors.initials: E
authors.lastname: Brunhage
authors.forename: Eugeen
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D051579:Neurogranin / Q000134:cerebrospinal fluid*; D013569:Synapses / Q000737:chemistry / Q000473:pathology*
chemical_list: D015415:Biomarkers; D051579:Neurogranin