Cited by 49Paraoxonase enzyme and polymorphismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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

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Zimetti, Francesca, Adorni, Maria Pia, Marsillach, Judit, Marchi, Cinzia, Trentini, Alessandro, Valacchi, Giuseppe, Cervellati, Carlo·2021·Oxidative Medicine and Cellular Longevity

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.

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Authors
Zimetti, F., Adorni, M. P., Marsillach, J., Marchi, C., Trentini, A., Valacchi, G., & Cervellati, C.
Affiliations
  • University of Parma (IT)
  • University of Washington (US)
  • University of Ferrara (IT)
  • North Carolina State University (US)
Corresponding author
Adorni, Maria Pia
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2021-01
Volume
2021
Issue
1
Pages
6695796-6695796
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
OpenAlex
W3119552585
Cited by
49
References
137
Citations by year
2026: 6 · 2025: 10 · 2024: 7 · 2023: 14 · 2022: 6 · 2021: 6
FWCI
1.08
Type
journal article
Language
en
Open access
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
Funders
National Institutes of Health (P50 AG05136)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
high-density lipoprotein, Alzheimer's disease, HDL proteome, glutathione peroxidase 3, paraoxonase 1, PON3, myeloperoxidase, serum amyloid A, oxidative stress, inflammation, antioxidant function, atherogenesis, vascular protection
MeSH terms
Alzheimer Disease, Animals, Anti-Inflammatory Agents, Antioxidants, Humans, Inflammation, Lipoproteins, HDL, Oxidative Stress

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