Apolipoprotein E Genotypic Frequencies Among Down Syndrome Patients Imply Early Unsuccessful Aging for ApoE4 Carriers

Forte, Giusi Irma; Piccione, Maria; Scola, Letizia; Crivello, Antonino; Galfano, Cristina; Corsi, Massimiliano M.; Chiappelli, Martina; Candore, Giuseppina; Giuffrè, Mario; Verna, Roberto; Licastro, Federico; Corsello, Giovanni; Caruso, Calogero; Lio, Domenico

doi:10.1089/rej.2006.0525

Cited by 15 publications

(9 citation statements)

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“…Furthermore, it becomes of interest to explore the geographical and ethnic allele distribution, which is extremely important in fully understanding the SNP variant effects. Precisely, Sicilian individuals have a specific genetic background and different allele distribution compared with the rest of Europe and with the rest of Italy (north–south genetic trend), due to distinct gene–environment interactions and, certainly, due to deep human migration movements, which have occurred in Sicily over the centuries as described by several authors [25-28]. …”

Section: Introductionmentioning

confidence: 99%

Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

et al. 2014

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IntroductionOsteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals.MethodsIn 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis.ResultsIn our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features.ConclusionsThis work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.

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Section: Introductionmentioning

confidence: 99%

Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

et al. 2014

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“…More recently APOE 4 genotype frequency has been found increased in subjects with DS [38]. Therefore, the above reported markers point out that DS may be considered a condition of accelerated ageing especially in those individual carrying a specific genetic make-up.…”

Section: Down Syndrome (Ds) and Chronic Inflammationmentioning

confidence: 87%

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Licastro¹,

Porcellini²

2017

Down Syndr Chr Abnorm

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IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence. Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...

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“…Infants carrying ε4 alleles have less white and gray matter in areas of the parietal and temporal lobes, but more frontal lobe matter (a phenomenon showing some thematic resemblance to PASA; Dean et al 2014). Despite its long-held connection to dementia onset in the DS population (Coppus et al 2008;Deb et al 2000;Forte et al 2007;Hardy et al 1994;Lai et al 1999;Lambert et al 1996;Prasher et al 1997Prasher et al , 2008Royston et al 1994Royston et al , 1996, APOE status might also affect the course of neurocognitive growth and decline in those with trisomy 21. Linear regression analysis of performance IQ from 5 to 30 years of age suggests that subgroups of individuals with DS positive for only ε2/ε3 are protected from worsening function compared to subgroups with an ε4 allele (Del Bo et al 1997).…”

Section: Apoe Statusmentioning

confidence: 99%

Assessing Cognitive Improvement in People with Down Syndrome: Important Considerations for Drug-Efficacy Trials

Fernandez

Reeves

2015

Cognitive Enhancement

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Experimental research over just the past decade has raised the possibility that learning deficits connected to Down syndrome (DS) might be effectively managed by medication. In the current chapter, we touch on some of the work that paved the way for these advances and discuss the challenges associated with translating them. In particular, we highlight sources of phenotypic variability in the DS population that are likely to impact performance assessments. Throughout, suggestions are made on how to detect meaningful changes in cognitive-adaptive function in people with DS during drug treatment. The importance of within-subjects evaluation is emphasized.

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Apolipoprotein E Genotypic Frequencies Among Down Syndrome Patients Imply Early Unsuccessful Aging for ApoE4 Carriers

Cited by 15 publications

References 40 publications

Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Assessing Cognitive Improvement in People with Down Syndrome: Important Considerations for Drug-Efficacy Trials

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