Low Levels of Soluble NG2 in Cerebrospinal Fluid from Patients with Dementia with Lewy Bodies

Article type: Research Article

Authors: Nielsen, Henrietta M.^a | Hall, Sara^{b; c} | Surova, Yulia^{b; c} | Nägga, Katarina^d | Nilsson, Christer^d | Londos, Elisabet^d | Minthon, Lennart^{d; e} | Hansson, Oskar^d | Wennström, Malin^{e; *}

Affiliations: [a] Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA | [b] Department of Clinical Sciences, Lund University, Lund, Sweden | [c] Department of Neurology, Skåne University Hospital, Lund, Sweden | [d] Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden | [e] Department of Clinical Sciences Malmö, Molecular Memory Research Unit, Lund University, Lund, Sweden

Correspondence: [*] Correspondence to: Malin Wennström, Department of Clinical Sciences Malmö, Molecular Memory Research Unit, The Wallenberg Lab, Lund University, 205 02 Malmö, Lund, Sweden. Tel.: +46 40 335733; E-mail: [email protected].

Abstract: The proteoglycan NG2 plays a major role in proliferation, migration, and differentiation of pericytes and NG2 cells in the brain. We have previously reported decreased soluble NG2 (sNG2) levels in cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and a relationship between sNG2 and AD biomarkers in these patients. To further investigate whether alterations in sNG2 is specific to AD pathology, we measured levels of sNG2 in CSF from a patient cohort consisting of non-demented controls (n = 51), patients with Parkinson's disease (PD) (n = 61), and patients with dementia with Lewy bodies (DLB) (n = 37), two synucleinopathies whereof the latter disorder frequently coincides with amyloid-β pathology similar to AD. We found decreased sNG2 concentrations in DLB patients, but not in PD patients, compared to controls. Levels of sNG2 in controls and PD patients correlated to T-tau, P-tau, α-synuclein, and neurosin. Only one correlation, between sNG2 and neurosin, was found in DLB patients. Analysis of a second cohort consisting of controls (n = 23) and DLB patients (n = 31) showed that the result was reproducible, as lower levels of sNG2 again were found in DLB patients compared to controls. We conclude that lower levels of sNG2 levels indicate a DLB-related impact on NG2 expressing cells foremost associated with neuropathology linked to accumulation of amyloid-β and not α-synuclein.

Keywords: α-synuclein, Alzheimer's disease markers, amyloid-β, biomarker, cerebrospinal fluid, dementia with Lewy bodies, NG2, neurosin, Parkinson's disease, synucleinopathies

DOI: 10.3233/JAD-132246

Journal: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 343-350, 2014