scholarly journals Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Francesco Panza ◽  
Davide Seripa ◽  
Grazia D'Onofrio ◽  
Vincenza Frisardi ◽  
Vincenzo Solfrizzi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Statistical Power ◽  
Psychological Symptoms ◽  
Late Onset ◽  
Neuropsychiatric Symptoms ◽  
Apoe Gene ◽  
Late Life Depression ◽  
Underlying Mechanisms ◽  
Apoe Genotypes

Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.

Race-Related Association between APOE Genotype and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Black People ◽  
Late Onset ◽  
Meta Analysis ◽  
Group Analysis ◽  
Apoe Genotype ◽  
Cochrane Library ◽  
Data Sets ◽  
Apoe Genotypes

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for 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.

scholarly journals Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease

2021 ◽  
Author(s):  
Roland Friedel ◽  
Yong Huang ◽  
Minghui Wang ◽  
Shalaka Wahane ◽  
Mitzy Ríos de Anda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Amyloid Plaque ◽  
Reactive Astrocytes ◽  
Glial Activation ◽  
Plaque Burden ◽  
Aβ Amyloid ◽  
Underlying Mechanisms

Abstract Communication between glial cells has a profound effect on the pathophysiology of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Here, we reveal a role of reactive astrocytes in enforcing cell distancing in the glial nets surrounding amyloid plaques, which restricts microglial coverage of Aβ, a prerequisite to detect and engulf amyloid deposits. This process is mediated through guidance receptor Plexin-B1, which we identified as a key network regulator of late-onset AD. We show that Plexin-B1 is robustly upregulated in plaque-associated astrocytes in a corona-like pattern, and its expression levels correlate with plaque burden and disease severity in AD patients. In APP/PS1 mice, an amyloidogenic model of AD, removing Plexin-B1 led to smaller peri-plaque glial nets with relaxed cell distancing and enhanced glial coverage of Aβ plaques, as well as transcriptional changes in both reactive astrocytes and disease-associated microglia that are linked to glial activation and amyloid clearance. Furthermore, amyloid plaque burden was lowered, together with a shift towards dense-core plaques and reduced neuritic dystrophy. Our data thus support a role of Plexin-B1 in controlling glial net structure by imposing cell distancing, leading to poor glial coverage of Aβ, reduced amyloid clearance and compaction. Relaxing cell distancing by targeting guidance receptors may present an alternative strategy to alleviate neuroinflammation in AD by improving glial coverage of Aβ amyloid and plaque compaction.

scholarly journals A SERUM PROTEIN SIGNATURE OF APOE GENOTYPES IN CENTENARIANS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
Stefano Monti ◽  
Stefano Monti ◽  
Paola Sebastiani ◽  
Anastasia Gurinovich ◽  
Toshiko Tanaka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Late Onset ◽  
Expression Profiles ◽  
Apoe Genotype ◽  
Cognitive Change ◽  
Serum Proteomics ◽  
Apoe Genotypes ◽  
Protein Signature

Abstract The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.

A NARRATIVE REVIEW OF THE MANAGEMENT OF BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

2021 ◽  
pp. 61-69
Author(s):  
Nimitha K J ◽  
Shailendra Mohan Tripathi ◽  
Porimita Chutia ◽  
Pooja Misal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alzheimer Disease ◽  
Rating Scale ◽  
Sleep Problems ◽  
Psychological Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Treatment Strategies ◽  
Sensory Stimulation ◽  
Mood Stabilizers

Dementia is a chronic or progressive neurodegenerative condition which is organic in origin. There will be impairment of thinking, memory orientation, comprehension, language, calculation, and judgement. Alzheimer's disease facts and gures in 2021 according to Alzheimer's association shows Alzheimer's disease accounts for 60% to 80% of the total cases. Behavioural and psychological symptoms of dementia also known as neuropsychiatric symptoms are a group of symptoms with behavioural and psychological manifestations. Disturbances include behavioural symptoms like wandering, hoarding, physical aggression, sexually disinhibition, culturally inappropriate behaviour, agitation and psychological symptoms like apathy, depression, anxiety, delusions, and hallucinations, sundowning, elation. Scales like the Neuropsychiatric Inventory, the Behavioural Pathology in Alzheimer Disease rating scale, the Consortium to Establish a Registry for Alzheimer Disease Behaviour Rating Scale for Dementia, Dementia Behaviour Disturbance scale, and the Neurobehavioral Rating Scale can be utilized to recognise BPSD.Neuropsychological assessment also have an important role. Non-pharmacological methodologies contain different sorts of treatment: tactile stimulation, pressure point massage, fragrant healing, light treatment, garden exercises, music therapy, dance therapy, and Snoezelen multisensory therapy, psychological strategies of multicomponent treatment strategies. Broadly focussing on sensory stimulation, social activities, structural activities, behavioural activities, environmental activities, and training programmes. Pharmacological treatment includes antipsychotics, mood stabilizers and antidepressants in treating BPSD, and cholinesterase inhibitors and memantine for the situation of Alzheimer's dementia sedative/hypnotics for sleep issues. Treatment can be further categorized based on individual NPS like agitation, psychosis, apathy, depression, sleep problems and other symptoms. Future treatment which has less evidence as of now includes rTMS, TDCS and Photo biomodulation therapy

scholarly journals Leveraging functional annotation to identify genes associated with complex diseases

2019 ◽  
Author(s):  
Wei Liu ◽  
Mo Li ◽  
Wenfeng Zhang ◽  
Geyu Zhou ◽  
Xing Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Complex Traits ◽  
Statistical Power ◽  
Late Onset ◽  
Disease Etiology ◽  
Expression Levels ◽  
Epigenetic Information ◽  
Disease Associated Genes

AbstractTo increase statistical power to identify genes associated with complex traits, a number of transcriptome-wide association study (TWAS) methods have been proposed using gene expression as a mediating trait linking genetic variations and diseases. These methods first predict expression levels based on inferred expression quantitative trait loci (eQTLs) and then identify expression-mediated genetic effects on diseases by associating phenotypes with predicted expression levels. The success of these methods critically depends on the identification of eQTLs, which may not be functional in the corresponding tissue, due to linkage disequilibrium (LD) and the correlation of gene expression between tissues. Here, we introduce a new method called T-GEN (Transcriptome-mediated identification of disease-associatedGens withEpigenetic aNnotation) to identify disease-associated genes leveraging epigenetic information. Through prioritizing SNPs with tissue-specific epigenetic annotation, T-GEN can better identify SNPs that are both statistically predictive and biologically functional. We found that a significantly higher percentage (an increase of 18.7% to 47.2%) of eQTLs identified by T-GEN are inferred to be functional by ChromHMM and more are deleterious based on their Combined Annotation Dependent Depletion (CADD) scores. Applying T-GEN to 207 complex traits, we were able to identify more trait-associated genes (ranging from 7.7 % to 102%) than those from existing methods. Among the identified genes associated with these traits, T-GEN can better identify genes with high (>0.99) pLI scores compared to other methods. When T-GEN was applied to late-onset Alzheimer’s disease, we identified 96 genes located at 15 loci, including two novel loci not implicated in previous GWAS. We further replicated 50 genes in an independent GWAS, including one of the two novel loci.Author summaryTWAS-like methods have been widely applied to understand disease etiology using eQTL data and GWAS results. However, it is still challenging to discriminate the true disease-associated genes from those in strong LD with true genes, which is largely due to the misidentification of eQTLs. Here we introduce a novel statistical method named T-GEN to identify disease-associated genes considering epigenetic information. Compared to current TWAS methods, T-GEN can not only identify eQTLs with higher CADD scores and function potentials in gene-expression imputation models, but also identify more disease-associated genes across 207 traits and more genes with high (>0.99) pLI scores. Applying T-GEN in late-onset Alzheimer’s disease identified 96 genes at 15 loci with two novel loci. Among 96 identified genes, 50 genes were further replicated in an independent GWAS.

scholarly journals Assessment of Behavioural and Psychological Symptoms Associated with Dementia

2007 ◽  
Vol 34 (S1) ◽  
pp. S67-S71 ◽  
Author(s):  
David Conn ◽  
Lilian Thorpe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Psychological Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Full Range ◽  
Behavior Rating ◽  
Neuropsychiatric Inventory ◽  
Behavior Rating Scale ◽  
Behavioral Pathology

Neuropsychiatric symptoms (mood, psychotic, and behavioural) are very common in dementia and do not necessarily correlate well with other measures of cognition. However, these symptoms are of great importance, as they are a major source of excess disability, patient distress and caregiver burden and have great impact on the level of care required, and the associated costs. This paper is a review of the most useful outcome measures for behaviour and mood symptoms. Investigators who require a comprehensive instrument to measure neuropsychiatric symptoms in studies of patients with dementia should consider using the Neuropsychiatric Inventory (NPI), the Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease (CERADBRSD) or, possibly, the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD). The Cornell Scale for Depression in Dementia and the Dementia Mood Assessment Scale (DMAS) are recommended for evaluating depressive symptoms and the Cohen-Mansfield Agitation Inventory (CMAI) is very useful for evaluating the full range of agitation symptoms.

Behavioral and Neuropsychiatric Outcomes in Alzheimer's Disease

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S18) ◽  
pp. 22-25 ◽  
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Psychological Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Caregiver Distress ◽  
Aspartate Receptor ◽  
Home Placement ◽  
Behavioral And Psychological Symptoms

AbstractBehavioral and psychological symptoms of dementia pose significant challenges in the management of patients with Alzheimer's disease. Neuropsychiatric symptoms are associated with cognitive decline, highly impaired activities of daily living, and frontal lobe pathology. Moreover, behavioral and psychological symptoms can diminish patient quality of life, increase caregiver distress, and accelerate nursing home placement. Although these symptoms are often associated with the later stages of Alzheimer's disease, a high percentage of individuals with mild cognitive impairment or mild Alzheimer's report symptoms as well. This article provides an overview of behavioral and neuropsychiatric symptoms associated with Alzheimer's disease and discusses nonpharmacologic and pharmacologic approaches to the management of such symptoms. For patients with severe behavioral and psychological symptoms of dementia, pychotropic agents may be warranted, whereas approved therapies for Alzheimer's, including cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine, may be appropriate in less severe cases.

scholarly journals Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Tariq Ahmad Masoodi ◽  
Sulaiman A. Al Shammari ◽  
May N. Al-Muammar ◽  
Adel A. Alhamdan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Late Onset ◽  
Apoe Gene ◽  
Tolerance Index ◽  
Nucleotide Polymorphisms ◽  
Mutant Type ◽  
Stability Change ◽  
Apoe Protein

Introduction. Apolipoprotein E (APOE) is an important risk factor for Alzheimer’s disease (AD) and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs) are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene.Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns) SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server.Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs) score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD) values were higher for three mutant-type structures compared to the native modeled structure.Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

Sign in / Sign up

Export Citation Format

Share Document