scholarly journals Correlation of [18F]florbetaben textural features and age of onset of Alzheimer’s disease: a principal components analysis approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Li ◽  
Emanuele Antonecchia ◽  
Marco Camerlenghi ◽  
Agostino Chiaravalloti ◽  
Qian Chu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Lobe ◽  
Principal Components ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Textural Features ◽  
Orbital Gyrus ◽  
The Right

Abstract Background When Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset. We aim at identifying [$$^{18}$$ 18 F]florbetaben PET biomarkers sensitive to differences between early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). We conducted [$$^{18}$$ 18 F]florbetaben PET/CT scans of 43 newly diagnosed AD subjects. We calculated 93 textural parameters for each of the 83 Hammers areas. We identified 41 independent principal components for each brain region, and we studied their Spearman correlation with the age of AD onset, by taking into account multiple comparison corrections. Finally, we calculated the probability that EOAD and LOAD patients have different amyloid-$$\beta$$ β ($$A\beta$$ A β ) deposition by comparing the mean and the variance of the significant principal components obtained in the two groups with a 2-tailed Student’s t-test. Results We found that four principal components exhibit a significant correlation at a 95% confidence level with the age of onset in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus. The data are consistent with the hypothesis that EOAD patients have a significantly different [$$^{18}$$ 18 F]florbetaben uptake than LOAD patients in those four brain regions. Conclusions Early-onset AD implies a very irregular pattern of $$A\beta$$ A β deposition. The authors suggest that the identified textural features can be used as quantitative biomarkers for the diagnosis and characterization of EOAD patients.

Early onset Alzheimer’s disease

2020 ◽  
pp. 75-82
Author(s):  
Ratnavalli Ellajosyula
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Geographical Location ◽  
Epidemiological Studies ◽  
Incidence Rates ◽  
Prevalence Rates ◽  
Early Onset Alzheimer’S Disease

The term ‘early onset Alzheimer’s disease’ (EOAD) is used when symptoms of Alzheimer’s disease (AD) occur in patients younger than 65 years. EOAD is an uncommon condition and data on epidemiology is limited. Prevalence rates range from 15 to 200 and incidence rates 2.4–22.6 per 100,000 population. Prevalence rates increase with age similar to that for late onset AD. The prevalence of autosomal dominant EOAD is 5.2 per 100,000. Half of these patients have an underlying mutation in amyloid precursor protein, presenilin 1 or 2 genes. Apolipoprotein E genotype is a risk factor for EOAD and homozygotes have an earlier age of onset. Methodological issues and geographical location make comparisons across epidemiological studies difficult. Further cross-national and cross-cultural studies with standardized methodology are necessary to understand the role of risk and protective factors, as well as to estimate the burden of the disease.

Progress in Molecular Genetics of Alzheimer's Disease

1996 ◽  
Vol 2 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Fuki M. Hisama ◽  
Gerard D. Schellenberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Positional Cloning ◽  
Age Of Onset ◽  
Late Onset ◽  
Chromosome 21 ◽  
Chromosome 1 ◽  
Amyloid Precursor Protein Gene ◽  
Chromosome 14

Recent intensive work has highlighted the genetic basis of several forms of Alzheimer's disease (AD). Mutations in the amyloid precursor protein gene on chromosome 21 can cause either an early-onset autosomal dominant AD or hereditary cerebral hemorrhage with amyloidosis. On chromosome 14, a second gene associated with 70 to 90% early-onset familial AD (FAD) was identified by positional cloning in 1995. Still other kindreds show no linkage to either chromosome 21 or chromosome 14; the third locus (on chromosome 1) was recently identified in affected descendants of a group of families known as the Volga Germans. In late-onset (age >65 years) AD, the apolipoprotein E gene allele ∊e4 on chromosome 19 has clearly been shown to be a risk factor for the development of AD and appears to modify the age of onset of the disease. The emerging picture is that AD is a genetically complex, heterogeneous disorder. Precisely how these genetic factors interact with each other and with other yet-to-be-identified genetic and nongenetic (environmental) factors to produce the clinical and pathologic findings in AD remains to be elucidated. The Neuroscientist 2:3–6, 1996

Effects of APOE, ACE, PICALM, and CYP2D6 Gene Variants on Alzheimer's Disease

2021 ◽  
Vol 17 ◽  
Author(s):  
Ozlem Oz ◽  
Gorsev Yener ◽  
Elcin Bora ◽  
Tufan Cankaya ◽  
Esra Ataman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Therapy Group ◽  
Acetylcholinesterase Inhibitor ◽  
Therapy Response ◽  
Treatment Groups ◽  
Risk Of Disease

Background: Alzheimer’s disease is a multifactorial, neurodegenerative disease which is considered the most common cause of dementia. It is divided into two subtypes based on the age of onset: early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). Objective: In this study, we aimed to analyse the polymorphisms of APOE2/E3/E4, ACE I/D, PICALM rs3851179, which are thought to increase the risk of disease, and CYP2D6 rs1080985, that affects the therapy response. Methods: 102 early onset and 99 late onset Alzheimer's patients diagnosed according to DSM-IV and NINCDS-ADRDA diagnostic criteria were included in the study. MMSE test was applied at the time of diagnosis and the control examination was performed after 6 months. We analysed the polymorphisms of APOE2/E3/E4 by fragment analysis and ACE I/D, PICALM rs3851179, CYP2D6 rs1080985 by Real Time- PCR. The response of the therapy and effects on prognosis were compared between groups by Mini-Mental State Exam test scores. Results: The score differences of the women were significantly lower than men’s score differences. The score differences of the EOAD group were significantly lower than the LOAD group in women. Family history situation was higher in men compared to women. The score differences were higher at CC genotype for PICALM rs3851179 in the EOAD group; the score differences were higher at E3/E4 genotype than E2/E2 genotype in LOAD. Also, the score differences were significantly higher at PICALM rs3851179 in the acetylcholinesterase inhibitor+antidepressant therapy group. Conclusions: The relationship between the treatment groups and related gene regions was investigated extensively for the first time in the literature. As a result, it will be a guide in the clinic in light of the findings of the prognosis and pharmacogenetic interactions of the disease obtained from the study.

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Nongenetic Factors as Modifiers of the Age of Onset of Familial Alzheimer's Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 337-349 ◽  
Author(s):  
Silvia Mejía ◽  
Margarita Giraldo ◽  
David Pineda ◽  
Alfredo Ardila ◽  
Francisco Lopera
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Early Onset ◽  
Age Of Onset ◽  
Univariate Analysis ◽  
Personal Factors ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
High Level

Objective: The purpose of this research was to identify environmental and personal factors that could be related to the variability in the age of onset of familial Alzheimer's disease (FAD) (36–62 years). Methods: A sample was taken of 49 subjects with FAD and with the mutation E280A in the presenilin-1 gene on chromosome 14; the sample was divided into two subgroups: 27 individuals with age of onset of the disease between 36 and 46 years (early onset) and 22 individuals whose disease began between 47 and 62 years (late onset). Information on environmental and personal factors was collected by means of a questionnaire answered by the patients if their clinical condition allowed it, or by their relatives; such information was organized in a categorical way. Comparisons between the two groups for each categorical variable were done by means of the chi-square test. Noncollinear variables that showed statistical significance were included as independent variables in a logistic regression analysis to predict their association with early onset of the disease. Results: Only 5 of the 140 studied variables were different between the two groups in univariate analysis: education, surgical history, type of stressful event, depression, and affective losses. The logistic regression model was constituted by education, depression, and affective losses. High-level education had approximately 15 times more probability of association with an early onset of the disease; both the history of affective losses and depressive symptoms had 4 times more probability of a similar association. Conclusions: The association of high-level education and early onset of the disease could be related to an earlier detection of symptoms, in turn determined by greater intellectual and environmental demands. The occurrence of depression and affective losses has been considered a prodromic manifestation of the disease. Our findings are evidence of high clinical heterogeneity even in a genetically homogeneous group.

scholarly journals The clinical utility of gene testing for Alzheimer’s disease

2011 ◽  
Vol 3 (1) ◽  
pp. 1 ◽  
Author(s):  
Emily R. Atkins ◽  
Peter K. Panegyres
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Genome Wide Association Studies ◽  
Apoe Ε4 ◽  
Gene Testing ◽  
A Genome

Alzheimer’s disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol- binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for lateonset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of lateonset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping.

scholarly journals HERPESVIRUS INFECTIONS AND CLINICAL-IMMUNOLOGIC INTERACTIONS IN PATIENTS WITH EARLY-ONSET ALZHEIMER’S DISEASE AND LATE-ONSET ALZHEIMER’S DISEASE

2021 ◽  
Vol 23 (4) ◽  
pp. 805-812
Author(s):  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
S. A. Krynskiy ◽  
N. A. Khailov ◽  
N. D. Selezneva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Viral Load ◽  
Early Onset ◽  
Late Onset ◽  
Adaptive Immune Response ◽  
Subsequent Development ◽  
Chronic Infections ◽  
Immune Parameters ◽  
Inflammatory Protein

Alzheimer’s disease (AD) is currently the most common cause of dementia. A significant role in the pathogenesis of AD belongs to the activation of the mechanisms of neuroinflammation. There is a hypothesis that chronic infections may play a role in the maintenance of the inflammatory response in AD. The aim of this work was to study the detection rate and DNA level of herpesviruses, as well as their possible relationship with the level of the key cytokines and with clinical parameters of AD in patients with early and late onset. 30 patients with AD and 33 healthy volunteers were enrolled. The quantitative determination of DNA of CMV, EBV, HHV-6, HHV-7 was carried out by PCR. The level of cytokines and soluble IL-1β antagonist (IL-1ra) in the blood was determined by ELISA. Herpesvirus infection with increased viral load was determined if at least one of the criteria was present: 1) DNA level of EBV and/or HHV-6 > 10,000 copies/ml in saliva; 2) presence of DNA of at least one of the EBV, HHV-6, HHV-7 viruses in the blood. In the subgroup of patients with early onset and increased viral load, there was a higher increase in the levels of a number of cytokines: proinflammatory IL-8 and IL-12, a Th2-cytokine IL-4, a cytokine of the adaptive immune response IL-2. However, the level of the anti-inflammatory protein IL-1ra was lower than in the controls. These changes may indicate a dysregulation of the antiviral response, with a predominance of activation of systemic inflammation and Th2-mediated reactions. Also, in early onset AD the increased viral load was associated with lower scores on Boston naming test. The results indicate that in studies of AD mechanisms and in the search for prognostic markers of the disease, it is important to take into account the heterogeneity of AD in terms of genetic predisposition factors, risk factors, immune parameters and clinical data. Such approach is necessary for the subsequent development of personalized approaches to the prevention and treatment of AD. 

scholarly journals Prevalence and Severity of Neuropsychiatric Symptoms in Early- Versus Late-Onset Alzheimer’s Disease

2019 ◽  
Vol 34 (7-8) ◽  
pp. 433-438 ◽  
Author(s):  
Sarah Baillon ◽  
Amy Gasper ◽  
Frances Wilson-Morkeh ◽  
Megan Pritchard ◽  
Amala Jesu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Functional Dependence ◽  
Neuropsychiatric Symptoms ◽  
Caregiver Distress ◽  
Duration Of Illness ◽  
Symptom Prevalence ◽  
Early Onset Alzheimer’S Disease

Background: The study aimed to compare neuropsychiatric symptoms (NPS) in people with early-onset Alzheimer’s disease (EOAD) and late-onset AD (LOAD). Methods: Fifty-six participants with LOAD and 24 participants with EOAD having mild dementia were assessed for NPS for their frequency, severity, and caregiver distress as measured by Neuropsychiatry Inventory (NPI) along with assessments of cognition and functional dependence. Results: Participants with EOAD and LOAD were not significantly different for total NPI score ( P = .057). Early-onset Alzheimer disease had greater prevalence of all the NPS except apathy. Participants with EOAD were significantly worse on anxiety ( P = .03), irritability ( P = .01), and sleep ( P < .01) subscales and their carers significantly more distressed by their irritability ( P = .002) and sleeping patterns ( P = .005). Regression analysis showed that higher NPI score was associated with longer duration of illness in EOAD and higher functional dependence in LOAD. Conclusions: The NPS severity was similar between EOAD and LOAD although EOAD had higher symptom prevalence and carer distress.

Sign in / Sign up

Export Citation Format

Share Document