Neuroscience Letters 492 (2011) 160–164 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Colocalisation of plasma derived apo B lipoproteins with cerebral proteoglycans in a transgenic-amyloid model of Alzheimer’s disease Virginie Lam, Ryusuke Takechi, Menuka Madhavi Sompala Pallebage-Gamarallage, Susan Galloway, John C.L. Mamo ∗ Curtin Health Innovation Research Institute, and The Australian Technology Network Centre for Metabolic Fitness, Curtin University, Bentley Campus, Kent Street, Perth 6102, Australia article info Article history: Received 17 November 2010 Received in revised form 28 January 2011 Accepted 1 February 2011 Keywords: Proteoglycans Alzheimer’s disease Amyloid beta Apolipoprotein B APP/PS1 transgenic mice abstract Alzheimer’s disease (AD) is characterized by cerebral proteinaceous deposits comprised of amyloid beta (A). Evidence suggests that enhanced blood-to-brain delivery of A occurs when plasma concentration is increased, exacerbating amyloidosis. In blood, significant A is associated with apolipoprotein (apo) B lipoproteins. In this study, immunofluorescent microscopy was utilised to explore if there is an association between apo B lipoproteins and proteoglycan expression within A-rich plaques in transgenic-amyloid mice. Focal accumulation of apo B was found with A-plaque in APP/PS1 mice. There was enrichment in the proteoglycans, agrin, perlecan, biglycan and decorin within the core of dense A-plaque. Perlecan, biglycan and decorin were positively associated with apo B lipoprotein abundance within amyloid plaque consistent with a cause-for-retention effect. These findings show that proteoglycans are an integral com- ponent of A deposits in APP/PS1 mice. This study suggests that some proteoglycans contribute to A retention, whilst other proteoglycans have different functions in the aetiology of AD. © 2011 Elsevier Ireland Ltd. All rights reserved. Amyloid beta (A), is a primary component of cerebral proteina- ceous deposits that are found within brain parenchyma in subjects with Alzheimer disease (AD) [39]. Neuronal cells synthesize A, however there is no evidence that accelerated biogenesis occurs in sporadic late onset AD, the most common form of this disor- der [6]. Cerebral A homeostasis is also dependent on degradation and clearance pathways that occur within the epithelial cells of the choroid plexus and via receptor mediated efflux of A on vascular endothelial cells, [28,38]. Several studies suggest that degradation and efflux of A may be impaired in subjects with AD, enhancing the propensity for A-oligomer formation to occur [5,7]. Amyloid- burden may also be exacerbated if cerebrovascular integrity is com- promised, a common pathological co-morbidity in subjects with AD. Recent studies showed exaggerated blood-to-brain delivery of A in amyloid transgenic mice and in wild-type mice and rabbits with dietary induced amplification of amyloidosis [30,31,11]. In blood, significant A is associated with apolipoprotein (apo) B lipoproteins of intestinal and hepatic origin [14,16], a pathway of amyloid biogenesis that is regulated by the ingestion of fats [10]. In wild-type mice, saturated fat-feeding and cholesterol feed- ing independently and synergistically compromise cerebrovascular integrity, resulting thereafter in exaggerated parenchymal infil- ∗ Corresponding author. Tel.: +61 8 9266 7232; fax: +61 8 9266 2358. E-mail address: J.Mamo@Curtin.edu.au (J.C.L. Mamo). tration and retention of apo B lipoprotein-associated-A [20,32]. Burgess et al. found in amyloid transgenic mice that the onset and progression of amyloidosis was positively associated with the plasma concentration of A [2]. The latter correlated with the hepatic and intestinal secretion of apo B-lipoproteins. Apo B immunoreactivity has been reported in the brain parenchyma of post-mortem AD subjects and models of AD [30,40,17]. Proteoglycans are major components of the extracellular matrix, characterized by a core protein to which glycosaminoglycan side chains are covalently attached [18]. Proteoglycans serve as bind- ing sites for receptors and as mediators of cell adhesion, migration and proliferation [18]. Proteoglycans, in particularly heparan sul- fate proteoglycans, have an important role in the pathogenesis of AD by enhancing the formation and stability of amyloid plaques [36]. However, their putative role in lipoprotein-A entrapment has not been considered. Agrin is an extracellular matrix HSPG pivotal for the develop- ment of the BBB [1]. Agrin exhibits structural similarity to perlecan [13], a proteoglycan reported to bind apo B lipoproteins in the hepatic sinusoidal space and murine models of atherosclerosis [33]. Perlecan, exhibits structural homology to the ligand binding region of the apo B/E lipoprotein receptor, the primary pathway for lipoprotein internalization [25,22]. Perlecan over-expression within the sub-endothelial space of coronary arteries has been implicated in the pathogenesis of atherosclerosis [15]. A number of studies have reported an increased abundance of agrin and per- 0304-3940/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2011.02.001