scholarly journals Altered Proteolysis in Fibroblasts of Alzheimer Patients with Predictive Implications for Subjects at Risk of Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Alessandra Mocali ◽  
Nunzia Della Malva ◽  
Claudia Abete ◽  
Vito Antonio Mitidieri Costanza ◽  
Antonio Bavazzano ◽  
...  
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Low Cost ◽  
Apoe Genotype ◽  
Normal Subjects ◽  
Culture Conditions ◽  
Cultured Fibroblasts ◽  
Laboratory Tool

There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer’s disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOEε4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a usefulin vitromodel for further studies on the pathogenetic process of AD.

Related Heterogeneity in Pathologically Confirmed Sporadic Alzheimer Disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011772
Author(s):  
Denis S Smirnov ◽  
Douglas Galasko ◽  
Annie Hiniker ◽  
Steven Edland ◽  
David P. Salmon
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Functional Decline ◽  
Apoe Genotype ◽  
Executive Dysfunction ◽  
Bimodal Distribution ◽  
Cognitive Testing ◽  
Apoe Ε4 ◽  
Age Related

Objective:To characterize age-related clinical heterogeneity in Alzheimer’s disease (AD) and determine if it is modified by APOE genotype or concomitant non-AD pathology, we analyzed data from 1750 patients with sporadic, pathologically-confirmed severe AD.Methods:In this retrospective cohort study, regression and mixed effects models assessed effects of estimated age of onset, APOE genotype, and their interaction on standardized clinical, cognitive and pathologic outcome measures from the National Alzheimer’s Coordinating Center (NACC) database.Results:A bimodal distribution of age of onset frequency in APOE ε4- cases showed best separation at age 63. Using this age cut-off, cases were grouped as early onset (EO) AD ε4- (n=169), EOAD ε4+ (n=273), late onset (LO) AD ε4- (n=511), and LOAD ε4+ (n=797). EOAD were more likely than LOAD patients to present with non-cognitive behavioral or motor symptoms or non-memory cognitive complaints, and had more executive dysfunction, but less language impairment on objective cognitive testing. Age of onset and ε4- genotype were independently associated with lower baseline MMSE and greater functional impairment, and EOAD had faster cognitive and functional decline than LOAD regardless of APOE genotype. EOAD were more likely than LOAD patients to receive a non-AD clinical diagnosis even though they were more likely to have “pure” AD without concomitant vascular or other non-AD neurodegenerative pathology.Conclusions:Early onset sporadic AD is associated with a greater likelihood of an atypical, non-memory dominant clinical presentation, especially in the absence of the APOE ε4 allele, which may lead to misattribution to non-AD underlying pathology.

Age, Age of Onset and Course of Primary Depressive Illness in the Elderly*

1983 ◽  
Vol 28 (2) ◽  
pp. 102-104 ◽  
Author(s):  
Martin G. Cole
Keyword(s):  
Elderly Patients ◽  
Depressive Episode ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
The Elderly ◽  
Depressive Illness ◽  
Physical Illness ◽  
Course Of Illness

Thirty-eight elderly patients with primary depressive illness (Feighner criteria) were followed up for 7–31 months. In the absence of persistent organic signs and severe physical illness, age of onset (first depressive episode after 60) but not age was significantly related to course of illness. Compared to early onset depressives, late onset depressives were more likely to remain completely well during the follow-up period and less likely to have frequent or disabling relapses.

Early and Late Onset Bipolar Disorders in Older Adults

2017 ◽  
Vol 41 (S1) ◽  
pp. S211-S211
Author(s):  
N. Smaoui ◽  
L. Zouari ◽  
N. Charfi ◽  
M. Maâlej-Bouali ◽  
N. Zouari ◽  
...  
Keyword(s):  
Older Adults ◽  
Bipolar Disorder ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Bipolar Disorders ◽  
Medical Diagnoses ◽  
The Mean ◽  
Bipolar Patients

IntroductionAge of onset of illness may be useful in explaining the heterogeneity among older bipolar patients.ObjectiveTo examine the relationship of age of onset with clinical, demographic and behavioral variables, in older patients with bipolar disorder.MethodsThis was a cross-sectional, descriptive and analytical study, including 24 patients suffering from bipolar disorders, aged 65 years or more and followed-up in outpatient psychiatry unit at Hedi Chaker university hospital in Sfax in Tunisia. We used a standardized questionnaire including socio-demographic, behavioral and clinical data. Age of onset was split at age 40 years into early-onset (< 40 years; n = 12) and late-onset (≥ 40 years; n = 12) groups.ResultsThe mean age for the entire sample was 68.95 years. The mean age of onset was 39.95 years. The majority (60%) of patients were diagnosed with bipolar I. Few meaningful differences emerged between early-onset and late-onset groups, except that tobacco use was significantly higher in the late-onset group (66.6% vs. 16.6%; P = 0.027). No significant differences between the early-onset and late-onset groups were seen on demographic variables, family history and number of medical diagnoses or presence of psychotic features.ConclusionOur study found few meaningful behavioral differences between early versus late age at onset in older adults with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Maternofetal outcomes in early versus late onset pre-eclampsia: a comparative study

2019 ◽  
Vol 8 (2) ◽  
pp. 548
Author(s):  
Poornima Shankar ◽  
Kavitha Karthikeyan ◽  
Amrita Priscilla Nalini ◽  
Sindhura M. ◽  
Gowtham Kim
Keyword(s):  
Risk Factors ◽  
Gestational Age ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Fetal Outcomes ◽  
Chi Square ◽  
Onset Type ◽  
Significant Difference ◽  
Early Onset Preeclampsia

Background: Preeclampsia is being increasingly recognized as two different entities: early-onset preeclampsia occurring at less than 34 weeks of gestation, and late-onset disease occurring at 34 or more weeks of gestation. Early-onset and late-onset pre-eclampsia are found to have different implications for the mother and neonate. The aim of this study is to compare the risk factors, maternal and fetal outcomes in early (<34 weeks) versus late (≥34weeks) onset preeclampsia.Methods: 208 patients diagnosed with pre-eclampsia in Chettinad Academy of Research and Education over a period of three years (From January 2014 to December 2016) were retrospectively studied. Patients were classified as early onset and late onset pre-eclampsia based on the gestational age of onset. Data on risk factors, maternal and fetal outcomes were collected and analyzed using Chi Square and Fisher’s test and compared.Results: The overall preeclampsia rate was 6.3%. Early onset and late onset were 34.6% and 65.3% respectively and the rate increased with increasing gestational age.35.3% of patients with late onset preeclampsia and 55.6% patients of early onset type required more than one drug which is a statistically significant difference. Proteinuria more than 3gm/l/day was significantly more in late onset preeclampsia than in early onset preeclampsia. 55.5% of patients with early onset pre-eclampsia required MgSO4 when compared to 17.4%. There was no statistically significant difference in the rate of caesarean section (61.1% vs 73.5%). Altered coagulation profile was significantly more in early onset preeclampsia (11.1%). The incidence of oligohydramnios, SGA and low APGAR at 5 minutes of birth were significantly high in early onset pre-eclampsia when compared to late onset type.Conclusions: Patients with early onset pre-eclampsia are found to have significantly higher rates of specific maternal and fetal morbidity when compared to the late onset type.

scholarly journals Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

2019 ◽  
Vol 20 (4) ◽  
pp. 968 ◽  
Author(s):  
Edurne Álvaro ◽  
Juana M. Cano ◽  
Juan L. García ◽  
Lorena Brandáriz ◽  
Susana Olmedillas-López ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Cpg Island ◽  
Low Frequency ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
Braf Mutations ◽  
Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

scholarly journals Priming of MSCs with inflammation-relevant signals affects extracellular vesicle biogenesis, surface markers, and modulation of T cell subsets

2020 ◽  
Author(s):  
Seth Andrews ◽  
Ty Maughon ◽  
Ross Marklein ◽  
Steven Stice
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Low Cost ◽  
Extracellular Vesicle ◽  
Culture Conditions ◽  
T Cell Subsets ◽  
Necrosis Factor Alpha

AbstractAlthough considerable evidence exists supporting the use of mesenchymal stromal cells (MSCs) for treating immune diseases, successful clinical translation has been challenging and has led researchers to investigate cell-free alternatives. MSC-derived extracellular vesicles (MSC-EVs) have been shown to mediate a significant portion of the observed therapeutic effect, including immunosuppression. MSCs have been shown to respond to different aspects of the injury microenvironment such as inflammatory cytokines and hypoxia, although acidosis has not been investigated and different conditions have not been assessed in terms of their effects on MSC-EV function. This study investigated the effects of acidosis, hypoxia, and inflammatory cytokine priming on MSCs and MSC-EVs. We cultured MSCs in the presence of acidosis, hypoxia, or inflammatory cytokines (Interferon-gamma and Tumor Necrosis Factor-alpha) and compared the characteristics of their EVs as well as their uptake by and suppression of different T cell subsets. MSCs showed a greater effect on suppressing activated CD4+ and CD8+ T cells than MSC-EVs. However, MSC-EVs from MSCs primed with acidosis increased CD4+ and CD8+ regulatory T cell frequency in vitro. This functional response was reflected by MSC-EV uptake. MSC-EVs from acidosis-primed MSCs were taken up by CD4+ and CD8+ regulatory T cells at a significantly higher level than MSC-EVs from control, hypoxic, and inflammatory cytokine groups. These data suggest that a simple low-cost alteration in MSC culture conditions, acidosis, can generate extracelluar vesicles that have a desirable influence on anti inflammatory T cell subtypes.

scholarly journals Whole-exome analysis in Parkinson’s disease reveals a high burden of ultra rare variants in early onset cases

2020 ◽  
Author(s):  
Bernabe I. Bustos ◽  
Dimitri Krainc ◽  
Steven J. Lubbe ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Rare Variants ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Late Onset ◽  
Genetic Component ◽  
Genetic Risk Assessment ◽  
Whole Exome

ABSTRACTParkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. We performed a “hypothesis-free” exome-wide burden-based analysis of different variant frequencies, predicted functional impact and age of onset classes, in order to expand the understanding of rare variants in PD. Analyzing whole-exome data from a total of 1,425 PD cases and 596 controls, we found a significantly increased burden of ultra-rare (URV= private variants absent from gnomAD) protein altering variants (PAV) in early-onset PD cases (EOPD, <40 years old; P=3.95×10−26, beta=0.16, SE=0.02), compared to LOPD cases (>60 years old, late-onset), where more common PAVs (allele frequencies <0.001) showed the highest significance and effect (P=0.026, beta=0.15, SE=0.07). Gene-set burden analysis of URVs in EOPD highlighted significant disease- and tissue-relevant genes, pathways and protein-protein interaction networks that were different to that observed in non-EOPD cases. Heritability estimates revealed that URVs account for 15.9% of the genetic component in EOPD individuals. Our results suggest that URVs play a significant role in EOPD and that distinct etiological bases may exist for EOPD and sporadic PD. By providing new insights into the genetic architecture of PD, our study may inform approaches aimed at novel gene discovery and provide new directions for genetic risk assessment based on disease age of onset.

scholarly journals Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease

2021 ◽  
Author(s):  
Maria del Carmen Moleon ◽  
Estrella Martinez-Gomez ◽  
Marisa Flook ◽  
Andreina Peralta-Leal ◽  
Juan Antonio Gallego ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Cross Sectional Study ◽  
Cytokine Profile ◽  
Sectional Study ◽  
Meniere Disease ◽  
Cross Sectional ◽  
Menière Disease

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, &lt;35 years old), and 39 with late onset MD (LOMD, &gt; 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1&beta; were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1&beta; were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

scholarly journals ANALYSIS OF THE ASSOCIATION OF BRONCHIAL ASTHMA CLINICAL COURSE WITH Arg16Gly POLYMORPHIC VARIANT IN THE β2-ADRENOCEPTOR GENE

2021 ◽  
Vol 17 (2) ◽  
pp. 70-76
Author(s):  
V.V. Kachkovska ◽  
L.N. Prystupa
Keyword(s):  
Bronchial Asthma ◽  
Early Onset ◽  
Clinical Course ◽  
Age Of Onset ◽  
Late Onset ◽  
Asthma Severity ◽  
Polymorphic Variant ◽  
Genotype Distribution ◽  
Significant Difference ◽  
Arg16gly Polymorphism

Relevance. The relevance of the study of Arg16Gly polymorphism of the β2-adrenoceptor (β2-AR) gene is due to the fact that a number of studies have proven its role in the development of bronchial asthma (BA), bronchial hyperactivity, the effectiveness of basic treatment. However, these associations show low reproducibility in various studies, so the question of the possibility of clinical application of the results of genetic testing for Arg16Gly polymorphic variant of the β2-AR gene remains unanswered. The main reasons why the clinical significance of this polymorphism is not confirmed in various studies are - population heterogeneity, insufficient sample size, improper characterization of comparison groups. Objective: to study the association of Arg16Gly polymorphism in the β2-adrenoceptor gene with BA clinical course taking into account the age of onset. Materials and methods. We examined 553 BA patients (group I included 282 patients with late-onset asthma and group II included 271 patients with early-onset asthma) and 95 apparently healthy individuals. The study has been approved by the Bioethics Committee of Medical Institute of Sumy State University. Arg16Gly polymorphism in the β2-АR gene (rs1042713) was determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results was performed using SPSS–17 program. Results. There was no significant difference in the distribution of genotypes for Arg16Gly polymorphism in the β2-AR gene depending on asthma severity with no regard for the age of onset (χ2 = 5.14; p = 0.27). With regard for the age of onset, we found out that early-onset BA was linked to a difference in genotype distribution for this polymorphic variant in patients with severe and non-severe course (χ2 = 14.76; р = 0.001). The frequency of Gly/Gly genotype was higher in patients with severe course (41.4%) as compared to patients with mild course (16.4%), while the frequency of Arg/Arg (32.9%) and Arg/Gly (50.7%) genotypes was higher in patients with mild asthma as compared to patients with severe course (24.3% and 34.3%). There was no significant difference in the distribution of genotypes in patients with late-onset asthma with regard to course severity (χ2 = 4.94; p = 0.084). The relative risk of severe course for early-onset asthma was 3.84 times higher (95% CI 2.11–7.36; p = 0.001) in the recessive model, 2.58 times higher (95% CI 1.53–4,37, p = 0.001) in the dominant model, and 2.16 times (95% CI 1.56–3.04) higher in the additive model. In patients with late-onset asthma, no association was found in all models. Conclusions. There was no significant difference in the distribution of genotypes for Arg16Gly polymorphism in the β2-AR gene depending on asthma severity with no regard for the age of onset. When adjusted for the age of onset, the analysis revealed a difference in genotype distribution for this polymorphic variant in patients with severe and non-severe course having early-onset BA (р = 0.001). The frequency of Gly/Gly genotype was higher in patients with severe course as compared to patients with mild course. For patients with late-onset asthma, no differences were found (p = 0.084). Heterozygous and homozygous Gly allele carriers have a higher risk of early-onset asthma only.

Clinical and Laboratory Differences Between Early-Onset and Late-Onset Adult Atopic Dermatitis

2020 ◽  
Vol 24 (4) ◽  
pp. 360-366
Author(s):  
Dae-Lyong Ha ◽  
Geun-Hwi Park ◽  
Hoon-Soo Kim ◽  
Hyun-Chang Ko ◽  
Moon-Bum Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Severity Index ◽  
Total Serum ◽  
Significant Difference ◽  
First Onset ◽  
Onset Group ◽  
Early Onset Group

Background Atopic dermatitis (AD) in adults is not uncommon, and its prevalence has been increasing in the recent decades. However, there is a paucity of data about the differences between early-onset and late-onset adult AD. Objective The objective of this study is to investigate the clinical and laboratory characteristics of adult AD, focusing on the differences between early-onset and late-onset adult AD. Methods We retrospectively reviewed the medical records and clinical photos of 214 adult AD patients (≥18 years of age) over a 3-year period. We classified the patients into 2 groups: early-onset (first onset of AD before 12 years of age) and late-onset (first onset of AD at 12 years of age or later). Results Among 214 patients, 151 patients (70.6%) belonged to the early-onset group (mean age 24.5 years), while 63 patients belonged to the late-onset group (mean age 29.5 years). An association with allergic asthma or rhinitis, a family history of atopic disease, elevated total serum IgE, and sensitivity to food allergens were more commonly seen in the early-onset group. The late-onset group had a significant likelihood of nonflexural involvement (38.1% vs 13.2%). There was no significant difference in the mean eczema area severity index score, eosinophil count, and sensitivity to aeroallergens between 2 groups. Conclusion Adult AD shows different clinical and laboratory characteristics depending on the age of onset. This study could help to create awareness about the heterogeneity of AD in adulthood and encourage further studies on clinical outcomes and different therapeutic methods depending on the age of onset.

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