Profile of dopamine metabolites in brain of WT and R6/2 mice at 4, 8 and 12 weeks of age.

<p>NS: non significant.</p

Barnes maze test in 6-week-old R6/2 and WT mice.

<p>Latency to reach the virtually target hole and numbers of pokes in the target hole were measured on day 5 (A) and day 12 (B). n = 20 animals/group.</p

HomeCageScan behaviours in R6/2 mice at age 4, 8 and 12 weeks.

<p>(A) Total time spent hanging, (B) grooming and (C) number of jumps, from the HomeCage recording. n = 20 animals/group.</p

Profile of serotonin metabolites in brain of WT and R6/2 mice at 4, 8 and 12 weeks of age.

<p>**p<0.001 compared to WT mice.</p

Elevation of GPNMB levels in CSF and brain of nGD patients.

<p>(A) Levels of GPNMB determined by LC-MS/MS in CSF of four type 3 GD patients. Results are means ± SEM. ** <i>p</i>< 0.01. (B) Levels of GPNMB in CSF of four type 3 GD patients determined by ELISA. Results are means ± SEM (n = 4). ** <i>p</i><0.01. (C) Western blot of GPNMB in CSF of control and a type 3 GD patient (sample designation 4). Results are from a typical experiment repeated 3 times. (D) Levels of GPNMB in nGD brain determined by ELISA(n = 3 for control, n = 6 for nGD (type 2 and type 3 patients). Results are means ± SEM, ** <i>p</i>< 0.01</p

GPNMB levels in brain and serum of Gba^flox/flox; nestin-Cre mice.

<p>Levels of GPNMB in (A) brain (n = 3) at different days post-natal (p) and (B) serum (n = 4,n = 5) of 21-day old Gba^flox/flox; nestin-Cre mice determined by ELISA. Results are means ± SEM *<i>P</i> < 0.05, **<i>P</i> < 0.01.</p

Up-regulated proteins in the CSF of type 3 GD patients.

<p>CSF from type 3 GD patients and age matched controls (n = 4) was digested with trypsin and subjected to label-free quantitative global proteomic analysis using liquid chromatography and tandem mass spectrometry (LC-MS/MS).</p><p>Up-regulated proteins in the CSF of type 3 GD patients.</p

Clinical information and correlation with GPNMB levels in the CSF of type 3 GD patients.

<p>* Full scale IQ</p><p>^# Arbitrary units</p><p>Clinical information and correlation with GPNMB levels in the CSF of type 3 GD patients.</p

Hyperphosphorylation of Tau in nGD samples.

<p>(A) Western blot of Tau and P-Tau (using two different anti-P-Tau antibodies) in brains of 21 day-old Gba^flox/flox; nestin-Cre mice and (B) P-Tau in the brain of one type 2 GD patient. Results are from a typical experiment repeated 3 times which gave similar results. GAPDH was used as a loading control. A molecular weight marker is shown (Mr = 55 kDa)</p

GPNMB peptides identified by LC-MS/MS.

<p>The GPNMB sequence is shown (UniProtKB/Swiss-Prot Q14956), with the site of cleavage [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120194#pone.0120194.ref020" target="_blank">20</a>] indicated in red and the two peptides identified by LC-MS/MS indicated in green and brown.</p