Abstract
Lipoprotein lipase (LPL) is involved in regulation of fatty acid metabolism, and facilitates cellular uptake of lipoproteins, lipids and lipid-soluble vitamins. We evaluated LPL distribution in healthy and Alzheimer’s disease (AD) brain tissue and its relative levels in cerebrospinal fluid. LPL immunostaining is widely present in different neuronal subgroups, microglia, astrocytes and oligodendroglia throughout cerebrum, cerebellum and spinal cord. LPL immunoreactivity is also present in leptomeninges, small blood vessels, choroid plexus and ependymal cells, Schwann cells associated with cranial nerves, and in anterior and posterior pituitary. In vitro studies have shown presence of secreted LPL in conditioned media of human cortical neuronal cell line (HCN2) and neuroblastoma cells (SK-N-SH), but not in media of cultured primary human astrocytes. LPL was present in cytoplasmic and nuclear fractions of neuronal cells and astrocytes in vitro. LPL immunoreactivity strongly associates with AD-related pathology, staining diffuse plaques, dystrophic and swollen neurites, possible Hirano bodies and activated glial cells. We observed no staining associated with neurofibrillary tangles or granulovacuolar degeneration. Granule cells of the dentate gyrus and the associated synaptic network showed significantly reduced staining in AD compared to control tissue. LPL was also reduced in AD CSF samples relative to those in controls.
Highlights
Lipoprotein lipase (LPL) is secreted as a homodimer and acts as a rate-limiting enzyme that releases fatty acids from mono, di- and triacylglycerides
LPL binds to the cell surface heparan sulfate proteoglycans, and forms a bridge between lipoprotein particles and cell surface receptors involved in lipoprotein particle uptake, which facilitates cellular uptake of lipoproteins, lipoproteinassociated lipids and lipophilic vitamins (Mead et al 2002)
LPL immunoreactivity was present in leptomeninges, where it associated with smooth muscle cells, endothelial cells, some arachnoid cells and microglia/macrophages (Fig. 1E)
Summary
Lipoprotein lipase (LPL) is secreted as a homodimer and acts as a rate-limiting enzyme that releases fatty acids from mono-, di- and triacylglycerides. LPL binds to the cell surface heparan sulfate proteoglycans, and forms a bridge between lipoprotein particles and cell surface receptors involved in lipoprotein particle uptake, which facilitates cellular uptake of lipoproteins, lipoproteinassociated lipids and lipophilic vitamins (Mead et al 2002) These functions of LPL are well-defined in the periphery. Numerous studies have shown that apoE-containing lipoproteins bind to the so-called LDL receptors in the brain, leading to lipid uptake (Pitas et al 1987; Lorent et al 1995; Fagan et al 1996). LPL-facilitated uptake of lipoproteins is potentially of high importance in the brain, because lipoprotein uptake by neuronal cells is relevant for structural and functional integrity of synapses (Mauch et al 2001; Göritz et al 2005; Fester et al 2009), and changes in lipoprotein metabolism have been shown to play a role in the pathogenesis of different brain diseases (Danik et al 1999; Hayashi, 2011)
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