Connection between the Altered HDL Antioxidant and Anti-Inflammatory Properties and the Risk to Develop Alzheimer’s Disease: A Narrative Review

Abstract

The protein composition of high-density lipoprotein (HDL) is extremely fluid. The quantity and quality of protein constituents drive the multiple biological functions of these lipoproteins, which include the ability to contrast atherogenesis, sustained inflammation, and toxic effects of reactive species. Several diseases where inflammation and oxidative stress participate in the pathogenetic process are characterized by perturbation in the HDL proteome. This change inevitably affects the functionality of the lipoprotein. An enlightening example in this frame comes from the literature on Alzheimer’s disease (AD). Growing lines of epidemiological evidence suggest that loss of HDL-associated proteins, such as lipoprotein phospholipase A2 (Lp-PLA2), glutathione peroxidase-3 (GPx-3), and paraoxonase-1 and paraoxonase-3 (PON1, PON3), may be a feature of AD, even at the early stage. Moreover, the decrease in these enzymes with antioxidant/defensive action appears to be accompanied by a parallel increase of prooxidant and proinflammatory mediators, in particular myeloperoxidase (MPO) and serum amyloid A (SAA). This type of derangement of balance between two opposite forces makes HDL dysfunctional, i.e., unable to exert its “natural” vasculoprotective property. In this review, we summarized and critically analyzed the most significant findings linking HDL accessory proteins and AD. We also discuss the most convincing hypothesis explaining the mechanism by which an observed systemic occurrence may have repercussions in the brain.

Long-Term Treatment of Cuban Policosanol Attenuates Abnormal Oxidative Stress and Inflammatory Response via Amyloid Plaques Reduction in 5xFAD Mice

“…ApoA-I and discoidal HDL was known to delay Aβ fibrillization in the brain through access via the blood-cerebrospinal fluid barrier at the choroid plexus [ 45 ]. It is well known that apoA-I and HDL can inhibit amyloid plaque aggregation and remove Aβ from the brain [ 45 , 46 ]. Moreover, in our study, PCO administration inhibited the formation of Aβ plaques, delaying AD pathology progression in 5xFAD mice.…”

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

“…Changes in the systemic environment such as inflammation are common in neurodegenerative diseases such as AD and Parkinson's Disease (PD) and can cause, along with oxidative stress, perturbances in the proteome composition of High-Density Lipoprotein (HDL) [47]. Circulating HDL provides resilience to cerebrovascular dysfunction in AD, which plays an important role in brain metabolism and homeostasis, dampening the clearance of Aβ and tau and thus leading to the formation of neuritic plaques and neurofibrillary tangles [48].…”

Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery

“…Loss of HDL-associated proteins with antioxidant action such apolipoprotein phospholipase A2, glutathione peroxidase-3, and paraoxonase (PON)-1 and -3 are supposed to be related to the early stage of AD. PON-3 modulating factors should be considered of interest in the study of potential AD treatments [ 147 ]. Additionally, Apolipoprotein A-I levels were decreased in serum of AD patients [ 148 ]…”

“…Protein profiling approach is considered a promising strategy to assess pathological changes in both asymptomatic AD and later stages of the disease [ 151 ]. In this approach, proteomic data collected from postmortem brain tissue of control, asymptomatic AD, and AD cases have been organized in groups or modules with biological significance in underlying the disease and correlated with clinical features of AD [ 147 ]. Alterations in these disease-associated modules are strongly conserved across AD cohorts [ 151 ].…”