title: Antioxidant status and APOE genotype as susceptibility factors for neurodegeneration in Alzheimer's disease and vascular dementia.
abstract: Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the ε4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes. To address this issue, we evaluated the effects of antioxidant status and APOE genotype on neurodegeneration in patients with dementia of the Alzheimer type (AD), with vascular dementia (VaD), and in elderly healthy controls. Eighty-two AD, 42 VaD patients, and 26 healthy controls were recruited and underwent medial temporal lobe atrophy (MTA) assessment, white matter hyperintensities rating (WMH), serum total antioxidant status assaying (TAS), and APOE genotyping. A logistic regression algorithm applied to our data revealed that a 0.01 mmol/L decrease of TAS concentration increased the probability of MTA by 24% (p=0.038) and that carriers of the APOE ε4 allele showed higher WMH scores (p=0.018), confirming that small variations in antioxidant systems homeostasis are associated with relevant modifications of disease risk. Furthermore, in individuals with analogous TAS values, the presence of the ε4 allele increased the predicted probability of having MTA. These outcomes further sustain the interaction of oxidative stress and APOE genotype to neurodegeneration.
authors.affiliation: Casa di Cura San Raffale Cassino & IRCCS San Raffale Pisana, Cassino, Italy. giancarlo.zito@afar.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Zito
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.forename: Valentina
authors.initials: V
authors.lastname: Panetta
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.forename: Carlo
authors.initials: C
authors.lastname: Salustri
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Siotto
authors.forename: Filomena
authors.initials: F
authors.lastname: Moffa
authors.forename: Claudia
authors.initials: C
authors.lastname: Altamura
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.forename: Domenico
authors.initials: D
authors.lastname: Lupoi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cassetta
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000975:Antioxidants / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D015140:Dementia, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E