LDL density and oxidation are modulated by pon1 promoter genotype in patients with Alzheimer's disease

Annachiara Cagnin, Alberta Leon, Daniela Vianello, Davide Colavito, Silvia Favaretto, Giulia Zarantonello, Anna Stecca, Mario Ermani, Alberto Zambon

Research output: Contribution to journalArticlepeer-review

Abstract

Cholesterol metabolism alteration is a hot topic in the field of Alzheimer's disease (AD). However, data on plasma lipoproteins cholesterol distribution and oxidation in AD and their possible genetic determinants are lacking. The paraoxonase-1 (PON1) gene -107C/T promoter polymorphisms have been found associated with AD. One of the fundamental functions of PON1 enzyme is the inhibition of low-density lipoproteins (LDL) oxidation. We therefore evaluated plasma lipoprotein profile and LDL density and oxidation in late-onset AD patients and healthy elderly subjects, without neuroimaging evidence of cerebrovascular lesions and not on lipid-lowering treatment, and their interaction with PON1 -107C/T and apolipoprotein E (APOE) genotypes. Mean plasma total cholesterol and LDL levels were higher in AD than controls (p <0.05). Lipoproteins cholesterol distribution shifted toward a greater prevalence of smaller, denser LDL (sd-LDL, p <0.05) only in AD patients with PON1 -107TT genotype, who also showed increased plasma levels of oxidized LDL (ox-LDL, p = 0.02). A significant association was observed between sd-LDL and ox-LDL levels (p <005) in AD patients. APOE genotype did not modulate lipoprotein distribution. Increased levels of sd-LDL and ox-LDL particles in the AD PON1 TT patients could be explained by the combined effect of an AD-related pro-oxidant milieu and an ineffective PON1 gene polymorphism-related antioxidant capacity. The functional correlate of the association between PON1 -107C/T polymorphism and AD may be the abnormal modulation of LDL oxidation. Ox-LDL may amplify the processes of endothelial injury promoted by vascular amyloid deposition, which represents one of the potential pathways explaining the cross-road between vascular and neurodegenerative pathomechanisms in AD.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalJournal of Alzheimer's Disease
Volume34
Issue number2
DOIs
Publication statusPublished - 2013

Keywords

  • Alzheimer's disease
  • cholesterol
  • lipoprotein profile
  • low-density- lipoproteins
  • oxidized LDL
  • paraoxonase
  • PON1 gene

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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