Expression pattern of perilipins in human brain during aging and in Alzheimer's disease

Abstract

Aims Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1–Plin5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. Methods We performed real‐time RT‐PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL‐6 expression was also performed. Results Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, whereas Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with early tauopathy or Alzheimer's disease and is associated with IL‐6 expression. Conclusions Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration.

Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson’s disease

“…Moreover, an accumulation of LD-containing cells (lipid-laden cells), associated with PLIN2 expression, was observed in meningeal, cortical and neurogenic brain regions of the aging mice [ 73 ]. Finally, a recent expression study on all human perlipin proteins (PLIN1-5), found that PLIN2 accumulates, particularly in neurons, in brains of old subjects and of patients with Alzheimer disease [ 74 ]. As an alternative putative mechanism regulating LD level, it was shown that targeted degradation of PLIN2 and PLIN3 occurs by chaperone-mediated autophagy (CMA) [ 75 ].…”

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

“…Consistently, lipid droplets (LDs), the organelles that serve as a storage of neutral lipids [64], accumulate in AD [65]. The expression of perilipin-2 (Plin2, a specific surface marker of LD), but not other perilipin family members, is selectively upregulated in the frontal cortex [66]. Increased neutral lipids and LDs in post-mortem AD brains, AD patient-derived fibroblasts [67], and peripheral blood mononuclear cells [68] collectively signify disrupted neutral lipid metabolism in AD (see reviews [69,70]).…”

Supplementation of Enriched Polyunsaturated Fatty Acids and CLA Cheese on High Fat Diet: Effects on Lipid Metabolism and Fat Profile

“…Regarding lipid metabolism, we observed a significant decrease of PLIN2 and PLIN3 expression in the ENR group. Very recently, it was demonstrated that PLIN2 in the brain is the only PLIN family member that is modulated with age and neuroinflammation, suggesting that PLIN2 may be connected with the brain, aging and inflammation [68]. Therefore, the decrease in PLIN2 expression in the ENR group suggests that PUFA ω-3 can prevent lipid accumulation and, consequently, possibly lipotoxicity and thus inflammation.…”