Cotransfected GFP diffusely stained axons (bottom panel). Fig. S3. Cbln1 or Cbln2 directly causes clustering

of NRX1β(S4+). Beads coated with HA-Cbln1, Cbln2, Cbln4, or CS-Cbln1 were incubated with HEK293 cells expressing NRX1β(S4+) for 2 days. Confocal images of HEK293 cells immunostained against NRX1β(S4+) (red or white) and beads (green) are shown. Scale bar, 25 μm. Fig. S4. Cbln1 serves as a direct presynaptic organizer in hippocampal neurons. (A) Accumulation of Navitoclax clinical trial functional presynaptic sites labeled with FM4-64 (red) around HA-Cbln1-coated beads (green). Scale bar, 20 μm. () Presynaptic sites were directly induced by HA-Cbln1-coated beads. Synapsin I-immunopositive terminals (red) were induced around HA-Cbln1-coated beads (arrowheads), which were located at extrasynaptic sites lacking endogenous AMPA receptors (detected by

anti-pan AMPA receptor antibody; green). Scale bar, 20 μm. Fig. S5. Cbln1 and Cbln2 but not Cbln4 induced presynaptic differentiation of cortical neurons. Beads coated with HA-Cbln1, Cbln2, Cbln4, or CS-Cbln1 were cocultured with cortical neurons. Confocal images of neurons immunostained for synapsin I (red or white) and beads (green) are shown. Scale bar, 20 μm. As selleck inhibitor a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer-reviewed and may be re-organized for online delivery, but are not copy-edited or typeset by Wiley-Blackwell. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. “
“Alzheimer’s disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular β-amyloid peptide (Aβ) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore

potential pathogenic links among some of these lesions, we examined β-secretase-1 (BACE1) alterations relative to Aβ deposition, neuritic pathology Metformin purchase and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and β-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for Aβ but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular Aβ IR among virtually all neuritic plaques, ranging from primitive to typical cored forms.