Article

Sorl1 as an Alzheimer's disease predisposition gene?

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Ariz., USA.
Neurodegenerative Diseases (impact factor: 3.06). 02/2008; 5(2):60-4. DOI:10.1159/000110789
Source: PubMed

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval.

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    Article: MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders.
    Olivier C Maes, Howard M Chertkow, Eugenia Wang, Hyman M Schipper
    [show abstract] [hide abstract]
    ABSTRACT: Understanding complex diseases such as sporadic Alzheimer disease (AD) has been a major challenge. Unlike the familial forms of AD, the genetic and environmental risks factors identified for sporadic AD are extensive. MicroRNAs are one of the major noncoding RNAs that function as negative regulators to silence or suppress gene expression via translational inhibition or message degradation. Their discovery has evoked great excitement in biomedical research for their promise as potential disease biomarkers and therapeutic targets. Key microRNAs have been identified as essential for a variety of cellular events including cell lineage determination, proliferation, apoptosis, DNA repair, and cytoskeletal organization; most, if not all, acting to fine-tune gene expression at the post-transcriptional level in a host of cellular signaling networks. Dysfunctional microRNA-mediated regulation has been implicated in the pathogenesis of many disease states. Here, the current understanding of the role of miRNAs in the central nervous system is reviewed with emphasis on their impact on the etiopathogenesis of sporadic AD.
    Current Genomics 05/2009; 10(3):154-68. · 2.41 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

AD predisposition
 
AD susceptibility factors
 
Alzheimer's disease
 
APOE gene
 
apolipoprotein E
 
association interval
 
extensively validated susceptibility gene
 
gene alleles
 
genetic load
 
genetically complex
 
large case-control whole-genome scan
 
late-onset AD
 
monogenic mutations cause early-onset AD
 
neurodegenerative disorder
 
neuronal sortilin-related receptor
 
non-cognitive behavioural symptoms
 
presents weak evidence
 
progressively disabling impairments
 
responsible
 
Sporadic AD