Abstract:
:Alzheimer's Disease (AD) is a neurodegenerative disorder with a complex aetiology displayed by multiple pathogenic factors. The APOE varepsilon4 allele represents the only established genetic risk factor for sporadic AD; in addition, previous findings on three single nucleotide polymorphisms (SNPs) located on the APOE promoter region, have led to a growing interest in their potential role in AD pathogenesis. The -491 A/T promoter polymorphism has been the one most frequently shown to be associated with AD, as it influences the APOE coding region transcription. The aim of this study was to evaluate the possible effect of the -491 A/T polymorphism on the cognitive profile of sporadic AD patients with a disease severity ranging from mild to moderate. Our results showed that patients carrying the -491 AA genotype had poorer cognitive performances than the -491 AT ones, statistically significant in demanding tests of visual attention, especially for the late-onset AD (LOAD). No further differences on cognitive profile were observed when stratifying AA and AT patients according to their APOE genotype. These results suggest a possible functional effect of the -491 A/T promoter on the neuropsychological performances of AD. This role seems to be independent of APOE genotype. In fact the effect of -491 A/T occurs predominantly on attention while the APOE varepsilon4 allele mainly affects memory performances. According to the biological effect exerted on APOE transcription, the -491 A/T polymorphism could be considered a disease modifier more than a risk factor for sporadic AD.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Valenza A,Bizzarro A,Marra C,Lauria A,Guglielmi V,Rossi C,Tiziano FD,Brahe C,Masullo Cdoi
10.1016/j.neulet.2010.02.004subject
Has Abstractpub_date
2010-03-26 00:00:00pages
199-203issue
3eissn
0304-3940issn
1872-7972pii
S0304-3940(10)00150-3journal_volume
472pub_type
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