APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

By

Doflein, Franz, 1873-1924
Nayyar, Ashima
Chakalova, Lubomira
Doflein, Franz, 1873-1924

Type

Article

Date of Publication

2015-9-24

Original Publication

Biodiscovery

Volume

17

Series / Issue

Issue: 17

Pages

1--17

Subjects

APOE , dementia , individual repair capacity. , Late-onset disease , mitochondrial DNA

Contributed by

Pensoft Publishers

Language

English

Published by

Newport on Tay Scottish Science Press

Identifiers

DOI: https://doi.org/10.7750/BioDiscovery.2015.17.1

 

Abstract

Dementia is very common in the elderly and its incidence increases in an age-dependent fashion. Alzheimer''s disease and vascular cognitive decline are the most common cases of dementia in the elderly. Amyloid burden and increased levels of oxidative damage have been implicated to play significant roles in the pathogenesis of late-onset dementia. In this paper we propose that there are three major genetic factors that may modulate the risk for dementia in later life: carriership of <em>APOE</em> variant alleles, carriership of mitochondrial DNA of haplogroups associated with ineffective oxygen utilisation (specifically, haplogroup H) and carriership of genetic polymorphisms conferring subtly deficient DNA repair. All three factors are quite common in the European populations. Each of these three factors may not have significant effect on the phenotype when taken separately, but when combined in the same genotype, the effects may be cumulative. Further studies are needed in order to elucidate the genotype-phenotype relationships and provide a reliable basis for assessment of the genetic risk for sporadic late-onset dementia. Lifestyle alterations and therapies targeted at decreasing the oxidative burden to aging cells and tissues may decrease the risk for neurological decline in later life.