Current Alzheimer research最新文献

{"title":"Disrupted White Matter Networks from Subjective Memory Impairment to Amnestic Mild Cognitive Impairment.","authors":"Wen Shao, Xuwen He, Xin Li, Wuhai Tao, Junying Zhang, Shujuan Zhang, Lei Wang, Yanan Qiao, Yu Wang, Zhanjun Zhang, Dantao Peng","doi":"10.2174/1567205018666210324115817","DOIUrl":"10.2174/1567205018666210324115817","url":null,"abstract":"<p><strong>Background and objective: </strong>Subjective memory impairment (SMI) is a preclinical stage prior to amnestic mild cognitive impairment (aMCI) along with the Alzheimer's disease (AD) continuum. We hypothesized that SMI patients had white matter (WM) network disruptions similar to those in aMCI patients.</p><p><strong>Methods: </strong>We used diffusion-tensor magnetic resonance imaging and graph theory to construct, analyze, and compare the WM networks among 20 normal controls (NC), 20 SMI patients, and 20 aMCI patients.</p><p><strong>Results: </strong>Compared with the NC group, the SMI group had significantly decreased global and local efficiency and an increased shortest path length. Moreover, similar to the aMCI group, the SMI group had lower nodal efficiency in regions located in the frontal and parietal lobes, limbic systems, and caudate nucleus compared to that of the NC group.</p><p><strong>Conclusion: </strong>Similar to aMCI patient, SMI patients exhibited WM network disruptions, and detection of these disruptions could facilitate the early detection of SMI.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"35-44"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25512537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APP/PS1 Gene-Environment Noise Interaction Aggravates AD-like Neuropathology in Hippocampus <i>Via</i> Activation of the VDAC1 Positive Feedback Loop.","authors":"Huimin Chi, Qingfeng Zhai, Ming Zhang, Donghong Su, Wa Cao, Wenlong Li, Xiaojun She, Honglian Yang, Kun Wang, Xiujie Gao, Kefeng Ma, Bo Cui, Yugang Qiu","doi":"10.2174/1567205018666210324114153","DOIUrl":"10.2174/1567205018666210324114153","url":null,"abstract":"<p><strong>Background: </strong>Environmental risk factors, including environmental noise stress, and genetic factors, have been associated with the occurrence and development of Alzheimer's disease (AD). However, the exact role and mechanism of AD-like pathology induced by environment-gene interactions between environmental noise and APP/PS1 gene remain elusive.</p><p><strong>Methods: </strong>Herein, we investigated the impact of chronic noise exposure on AD-like neuropathology in APP/PS1 transgenic mice. The Morris water maze (MWM) task was conducted to evaluate AD-like changes. The hippocampal phosphorylated Tau, amyloid-β (Aβ), and neuroinflammation were assessed. We also assessed changes in positive feedback loop signaling of the voltage-dependent anion channel 1 (VDAC1) to explore the potential underlying mechanism linking AD-like neuropathology to noise-APP/PS1 interactions.</p><p><strong>Results: </strong>Long-term noise exposure significantly increased the escape latency and the number of platform crossings in the MWM task. The Aβ overproduction was induced in the hippocampus of APP/PS1 mice, along with the increase of Tau phosphorylation at Ser396 and Thr231 and the increase of the microglia and astrocytes markers expression. Moreover, the VDAC1-AKT (protein kinase B)-GSK3β (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure.</p><p><strong>Conclusion: </strong>Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"14-24"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25512616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Amyloid is an Immunopeptide and Alzheimer's is an Autoimmune Disease.","authors":"Donald F Weaver","doi":"10.2174/1567205018666211202141650","DOIUrl":"https://doi.org/10.2174/1567205018666211202141650","url":null,"abstract":"<p><strong>Background: </strong>As new biomolecular targets for Alzheimer's disease (AD) emerge, there is a tendency to regard these as mutually exclusive and in competition, culminating in declarations that since the \"amyloid hypothesis is dead\" it needs to be replaced by completely different theories. However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation mechanisms of AD into a more widely-encompassing immunopathic model of AD could accomplish such a goal-a goal which could be achieved by repositioning the role of Aβ as an immunopeptide.</p><p><strong>Conclusion: </strong>This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities, Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies the broad definition of cytokine-the prototypic immunopeptide subtype. In addition to these immunoactivities, Aβ is also directly and independently cytotoxic to neurons by both necrotic and apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host neurons-an autoimmune event.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 11","pages":"849-857"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39686387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Model to Identify Alzheimer's Disease and Related Syndromes in Administrative Data.","authors":"Adeline Gallini,&nbsp;David Jegou,&nbsp;Maryse Lapeyre-Mestre,&nbsp;Anaïs Couret,&nbsp;Robert Bourrel,&nbsp;Pierre-Jean Ousset,&nbsp;D Fabre,&nbsp;Sandrine Andrieu,&nbsp;Virginie Gardette","doi":"10.2174/1567205018666210416094639","DOIUrl":"https://doi.org/10.2174/1567205018666210416094639","url":null,"abstract":"<p><strong>Background: </strong>Administrative data are used in the field of Alzheimer's Disease and Related Syndromes (ADRS), however their performance to identify ADRS is unknown.</p><p><strong>Objective: </strong>i) To develop and validate a model to identify ADRS prevalent cases in French administrative data (SNDS), ii) to identify factors associated with false negatives.</p><p><strong>Methods: </strong>Retrospective cohort of subjects ≥ 65 years, living in South-Western France, who attended a memory clinic between April and December 2013. Gold standard for ADRS diagnosis was the memory clinic specialized diagnosis. Memory clinics' data were matched to administrative data (drug reimbursements, diagnoses during hospitalizations, registration with costly chronic conditions). Prediction models were developed for 1-year and 3-year periods of administrative data using multivariable logistic regression models. Overall model performance, discrimination, and calibration were estimated and corrected for optimism by resampling. Youden index was used to define ADRS positivity and to estimate sensitivity, specificity, positive predictive and negative probabilities. Factors associated with false negatives were identified using multivariable logistic regressions.</p><p><strong>Results: </strong>3360 subjects were studied, 52% diagnosed with ADRS by memory clinics. Prediction model based on age, all-cause hospitalization, registration with ADRS as a chronic condition, number of anti-dementia drugs, mention of ADRS during hospitalizations had good discriminative performance (c-statistic: 0.814, sensitivity: 76.0%, specificity: 74.2% for 2013 data). 419 false negatives (24.0%) were younger, had more often ADRS types other than Alzheimer's disease, moderate forms of ADRS, recent diagnosis, and suffered from other comorbidities than true positives.</p><p><strong>Conclusion: </strong>Administrative data presented acceptable performance for detecting ADRS. External validation studies should be encouraged.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 2","pages":"142-156"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38902507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial Effects of Choline Alphoscerate on Amyloid-β Neurotoxicity in an In vitro Model of Alzheimer's Disease.","authors":"Chiara Burgaletto,&nbsp;Giulia Di Benedetto,&nbsp;Antonio Munafò,&nbsp;Renato Bernardini,&nbsp;Giuseppina Cantarella","doi":"10.2174/1567205018666210608093658","DOIUrl":"https://doi.org/10.2174/1567205018666210608093658","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most common form of neurodegenerative disorder characterized by cognitive impairment, which represents an urgent public health concern. Given the worldwide impact of AD, there is a compelling need for effective therapies to slow down or halt this disorder.</p><p><strong>Objective: </strong>Choline alphoscerate (α-GPC) represents a potentially effective cholinergic neurotransmission enhancing agent with an interesting clinical profile in cognitive dysfunctions improvement, although only scanty data are available about the mechanisms underlying such beneficial effects.</p><p><strong>Methods: </strong>The SH-SY5Y neuronal cell line, differentiated for 1 week with 10 μm of all-trans-retinoic acid (RA), to achieve a switch towards a cholinergic phenotype, was used as an in vitro model of AD. SH-SY5Y cells were pre-treated for 1h with α-GPC (100nM) and treated for 72 h with Aβ25-35 (10μM).</p><p><strong>Results: </strong>α-GPC was able to antagonize Aβ25-35 mediated neurotoxicity and attenuate the Aβ-induced phosphorylation of the Tau protein. Moreover, α-GPC exerted its beneficial effects by employing the NGF/TrkA system, knocked down in AD and, consequently, by sustaining the expression level of synaptic vesicle proteins, such as synaptophysin.</p><p><strong>Conclusion: </strong>Taken together, our data suggest that α-GPC can have a role in neuroprotection in the course of toxic challenges with Aβ. Thus, a deeper understanding of the mechanism underlying its beneficial effect, could provide new insights into potential future pharmacological applications of its functional cholinergic enhancement, with the aim to mitigate AD and could represent the basis for innovative therapy.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 4","pages":"298-309"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39075436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's Symptoms and Caregiver Affiliate Stigma: A Multinational Study.","authors":"Richard S Henry,&nbsp;Paul B Perrin,&nbsp;Sarah K Lageman,&nbsp;Teresita Villaseñor,&nbsp;Annahir N Cariello,&nbsp;Mickeal Pugh,&nbsp;Erin R Smith,&nbsp;Monica Arroyo,&nbsp;Alejandra Zarate,&nbsp;Judith Avila,&nbsp;Jose A Soto-Escageda","doi":"10.2174/1567205018666210608100917","DOIUrl":"https://doi.org/10.2174/1567205018666210608100917","url":null,"abstract":"<p><strong>Background and objective: </strong>Research has documented the stigma that individuals with degenerative neurological diseases experience, but caregivers also experience stigma by association (i.e., affiliate stigma). In order to shed light on the stigma of caregivers of people with degenerative neurological diseases, the current study aimed to explore cross-cultural differences in the prevalence of Parkinson's disease (PD) caregiver affiliate stigma, as well as the relationship between PD symptoms and caregiver affiliate stigma. Applications for Alzheimer's disease are discussed.</p><p><strong>Methods: </strong>Survey data were collected in PD clinics at public, academic medical centers. Informal caregivers of an individual with PD from the US (n = 105) and from Mexico (n = 148) participated in the study. Caregivers completed a questionnaire that included the MDS Unified PD Rating Scale to describe the symptoms of the individual with PD, as well as the Affiliate Stigma Scale and demographic information.</p><p><strong>Results: </strong>A series of multiple regressions was run to examine whether PD symptoms were associated with affiliate stigma and if these differed by country. These regressions suggested that different patterns of PD symptoms predicted affiliate stigma in each country. Stigma was higher in the US compared to Mexico, and the relationship between bowel/bladder symptoms and affiliate stigma was significantly stronger in the US.</p><p><strong>Conclusion: </strong>Symptoms of individuals with neurodegenerative diseases are related to affiliate stigma experienced by caregivers, and these relationships may differ cross-culturally. Negative public attitudes concerning bowl and bladder issues and the physical symptoms that accompany PD remain a source of stigma for caregivers and families, particularly in the US. Interventions for caregivers of individuals with neurodegenerative diseases should include strategies for coping with stigma concerning bladder and bowel problems, as well as other physical and mental health issues.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 3","pages":"222-231"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39075437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reading Fluency in Spanish Patients with Alzheimer's Disease.","authors":"María Del Carmen Pérez-Sánchez,&nbsp;María González-Nosti,&nbsp;Fernando Cuetos,&nbsp;Carmen Martínez,&nbsp;Marta Álvarez-Cañizo","doi":"10.2174/1567205018666210608102012","DOIUrl":"https://doi.org/10.2174/1567205018666210608102012","url":null,"abstract":"<p><strong>Background: </strong>Reading fluency is essential for our functioning in the literate society in which we live. Reading expressiveness or prosody, along with speed and accuracy, are considered key aspects of fluent reading. Prosodic patterns may vary, not being the same in children learning to read as in adulthood. But little is known about the prosodic characteristics and reading fluency of people with neurodegenerative diseases that causes language impairment and reading difficulties, such as Alzheimer's disease (AD).</p><p><strong>Objective: </strong>The aim of this work was to study reading fluency in AD, considering reading speed, accuracy and reading prosody.</p><p><strong>Methods: </strong>The participants were 20 healthy elderly Spanish adults, and 20 AD patients, aged 64-88 years. An experimental text was designed, that included declarative, exclamatory, and interrogative sentences, words with different stresses and low-frequency words. The reading of the participants was recorded and analyzed using Praat software.</p><p><strong>Results: </strong>The AD group showed significantly longer reading duration, both at the syllable level and at the word and sentence level. These patients also committed more pauses between words, which were also longer, and more reading errors. The control group showed a variation of the syllabic F0 in the three types of sentences, while these variations only appeared in declarative ones in the AD group.</p><p><strong>Conclusion: </strong>The pauses, along with the slight pitch variations and the longer reading times and errors committed, compromise the reading fluency of people with AD. Assessment of this reading feature could be interesting as a possible diagnostic marker for the disease.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 3","pages":"243-255"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39075438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Neuropsychiatric Symptoms of Parkinson's Disease with Measures of Striatal Dopaminergic Deficiency.","authors":"Ram Bishnoi,&nbsp;Marina C Badir,&nbsp;Sandarsh Surya,&nbsp;Nagy A Youssef","doi":"10.2174/1567205018666210827122133","DOIUrl":"https://doi.org/10.2174/1567205018666210827122133","url":null,"abstract":"<p><strong>Background: </strong>The role of nigrostriatal dopaminergic neurons degeneration is well established in the pathophysiology of Parkinson's disease. However, it is unclear if and how the degeneration of the dopamine pathways affects the manifestation of the neuropsychiatric symptoms (NPS) of Parkinson's Disease (PD). Dopamine transporter (DAT) imaging, a technique to measure the reduction in dopamine transporters is increasingly used as a tool in the diagnosis of PD.</p><p><strong>Methods: </strong>In this study, we examine if the baseline dopamine transporter density in the striatum measured by the Striatal Binding Ratio (SBR) is associated with the longitudinal onset and/or progression of NPS in PD as measured by part 1 of Movement Disorder Society - Unified Parkinson's Disease Rating Scale, over four years. Data of patients with PD and an abnormal screening present on 123I-ioflupane single-proton emission computed tomography were obtained from Parkinson's Progression Markers Initiative (PPMI) database. Latent Growth Modeling (LGM), a statistical technique that can model the change over time while considering the variability in the rate of change at the individual level, was used to examine the progression of NPS over time.</p><p><strong>Results: </strong>The results indicate the SBR did not correlate with the baseline NPS but did correlate with the rate of change of NPS (p<0.001) over the next four years, even after eliminating age-related variance, which can be a significant confounding factor.</p><p><strong>Conclusion: </strong>In conclusion, this study showed gradual worsening in NPS in patients with Parkinson's disease, which inversely correlates with the density of the dopamine transporters as measured by SBR at baseline.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 6","pages":"499-504"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39363483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer's-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics.","authors":"Miao Sun,&nbsp;Wenchenyang Bao,&nbsp;Chengyu Huang,&nbsp;Ziyue Xia,&nbsp;Changliang Zhang,&nbsp;Guangxian Wang,&nbsp;Runxin Wang,&nbsp;Jiangyu Li,&nbsp;Shaun Roux,&nbsp;Qian Li,&nbsp;Dongmei Zou,&nbsp;Kai Ma,&nbsp;Xiaofeng Bao","doi":"10.2174/1567205018666211022091110","DOIUrl":"https://doi.org/10.2174/1567205018666211022091110","url":null,"abstract":"<p><strong>Background: </strong>The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, including depression, anxiety, and Alzheimer's Disease (AD) and the use of probiotics as therapy for these diseases remains promising. However, the mechanisms underlying the gut microenvironment's influence on disease pathogenesis and therapy remain unclear.</p><p><strong>Objective: </strong>The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD.</p><p><strong>Methods: </strong>BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and functional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Protein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and correlate the changes with the above described measures.</p><p><strong>Results: </strong>Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-induced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed attenuated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature dendritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neuroinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of \"beneficial\" bacteria.</p><p><strong>Conclusion: </strong>Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 7","pages":"558-572"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39540506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of apolipoprotein E genotype for β-amyloid status prediction.","authors":"Carmen Peña-Bautista,&nbsp;Lourdes Álvarez-Sánchez,&nbsp;Lorena García,&nbsp;Miguel Baquero,&nbsp;Consuelo Cháfer-Pericás","doi":"10.2174/1567205019666211223141524","DOIUrl":"https://doi.org/10.2174/1567205019666211223141524","url":null,"abstract":"<p><strong>Background: </strong>Apolipoprotein E (ApoE) is the major genetic risk factor for sporadic Alzheimer's Disease (AD). Some studies showed a relationship between ApoE4 genotype and the cerebrospinal fluid (CSF) biomarkers (β-amyloid42, p-Tau, t-Tau), as well as with cognitive status. In this sense, it could be interesting to develop an approach to establish amyloid status in a minimally invasive way.</p><p><strong>Methods: </strong>The present study assessed the ApoE genotype in different participant groups (mild cognitive impairment due to AD (MCI-AD), mild/moderate dementia due to AD, MCI not due to AD (MCI not AD), other neurological diseases, healthy participants) (n = 342).</p><p><strong>Results: </strong>As expected, the ApoE4 allele was more prevalent in AD patients, characterized by impairment in CSF β-amyloid42 levels (Aβ +), than in the other groups (Aβ -). In this sense, ApoE4-carrier subjects showed lower CSF levels for β-amyloid42 and higher CSF levels for t-Tau and p-Tau. From this, a multivariate model to predict Aβ status was developed by means of partial least square analysis (PLS) and predictive variables (ApoE genotype, cognitive score, sex, age). This model showed suitable AUC-ROC 0.792 (95% CI, 0.744-0.840) and predictive negative value (81.6%).</p><p><strong>Conclusion: </strong>ApoE genotype could be useful in detecting CSF β-amyloid42 impairment associated with early AD development.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"18 13","pages":"1032-1040"},"PeriodicalIF":2.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39759665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}