Journal of Alzheimer's disease reports最新文献

{"title":"Study on cognitive impairment evaluation based on photoelectric neural information.","authors":"Zehua Wang, Ye Zhang, Ning Ma, Huiting Qiao, Meiyun Xia, Deyu Li","doi":"10.1177/25424823251325537","DOIUrl":"10.1177/25424823251325537","url":null,"abstract":"<p><strong>Background: </strong>Whether there is a cognitive load-dependent brain activation pattern in the pre-Alzheimer's disease phase is unknown. Multimodal system provides a powerful technical tool.</p><p><strong>Objective: </strong>We evaluated brain activity patterns under different cognitive loads in patients with mild cognitive impairment.</p><p><strong>Methods: </strong>Functional near-infrared spectroscopy signals and electroencephalography signals were acquired from the mild cognitive impairment group (MCI, n = 20) and the healthy control group (HC, n = 24) under four cognitive loads. We analyzed the respective brain activity features and performed correlation analyses.</p><p><strong>Results: </strong>(1) During the encoding phase, both the left occipital (<i>p</i> _cond= 0.05, <i>p</i> _group< 0.01) and left temporal (<i>p</i> _cond= 0.02, <i>p</i> _group= 0.03) skewness condition effects and between-group effects were significant. (2) As the cognitive load increased, the clustering coefficients and local efficiencies were significantly lower for the HC group. (3) The left occipital and left temporal activation skewness in the MCI group were significantly correlated with left occipital electrical features, whereas the left occipital activation intensity and skewness were significantly correlated with left occipital electrical features in HC group.</p><p><strong>Conclusions: </strong>The pattern of brain activity in MCI depends on cognitive load. Left occipital and left temporal may be important brain regions for evaluating MCI and need to be focused on in the future.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251325537"},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of coagulation factors on the risk of Alzheimer's disease: A Mendelian randomization study.","authors":"Wenzhi Shi, Juanjuan Lu, Peiyao Wei, Pingping Ning, Jiaxin Fan, Shan Huang, Xingzhi Guo, Rui Li","doi":"10.1177/25424823251327674","DOIUrl":"10.1177/25424823251327674","url":null,"abstract":"<p><strong>Background: </strong>Observational studies indicate a complex relationship between coagulation factors and Alzheimer's disease (AD). However, the current findings are inconsistent, and it remains uncertain whether a causal relationship exists.</p><p><strong>Objective: </strong>This study utilizes a Mendelian randomization analysis to investigate the causal relationships between blood levels of coagulation factors and AD risk.</p><p><strong>Methods: </strong>Eleven coagulation factors with valid instrumental variables available were evaluated. Two independent cohorts of European ancestry with AD genome-wide association study (GWAS) summary statistics were used: UK Biobank (UKB, N = 472,868) and the International Genomics of Alzheimer's Project (IGAP, N = 63,926). We primarily conducted Mendelian randomization (MR) analyses using the Inverse variance weighted (IVW). Meanwhile, the MR-Egger intercept test is used to detect horizontal pleiotropy, the Residual Sum of Squares observed (RSSobs) is used to assess the model's goodness of fit, and the leave-one-out analysis is employed for sensitivity analysis.</p><p><strong>Results: </strong>Using IVW analysis, the UKB database shows positive correlations of Protein C (PC, p = 0.002), Activated Partial Thromboplastin Time (aPTT, p = 0.019), and coagulation factor X (FX, p = 0.032) with AD, and a negative association for coagulation factor XI (FXI, p = 0.021). The IGAP database mirrors these findings for PC and FXI but not for the others. Leave-one-out analysis showed an anomaly after a single single nucleotide polymorphism (SNP) driving, yet the overall results remained stable.</p><p><strong>Conclusions: </strong>This study demonstrates that elevated levels of PC, FX, and aPTT, along with reduced levels of FXI, are causally associated with an increased risk of AD. These findings might pave the way for the diagnosis and treatment of AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251327674"},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying reversible psychiatric dementia mimics in new memory clinic outpatients.","authors":"Michitaka Funayama, Shin Kurose, Taketo Takata, Hiroyo Sato, Naoki Izawa, Kazuo Isozumi, Yumi Abe","doi":"10.1177/25424823251329804","DOIUrl":"10.1177/25424823251329804","url":null,"abstract":"<p><strong>Background: </strong>Timely identification of reversible conditions that mimic dementia is critical in memory clinic practice. However, psychiatric conditions as potential dementia mimics have not been studied as thoroughly as neurological ones, and detailed data on their reversibility remain limited.</p><p><strong>Objective: </strong>To identify reversible psychiatric dementia mimics.</p><p><strong>Methods: </strong>A retrospective chart review was conducted on 749 new outpatients to investigate etiologies, progression rates, a neuropsychological assessment, cognitive and functional levels, and potential reversibility, categorized by psychiatric and neurological conditions. Cases showing cognitive reversibility following treatment were also identified. Comparisons were made based on the presence or absence of potential reversibility, as well as actual reversibility.</p><p><strong>Results: </strong>Among the 749 individuals, 121 (16.2%) had potentially reversible conditions: 75 psychiatric and 46 neurological. Psychiatric conditions included depression, schizophrenia and delusional disorders, developmental disorders, alcohol use disorder, and dissociative and anxiety disorders. Compared to individuals without potentially reversible conditions, individuals with psychiatric conditions were younger, had a faster progression rate, and demonstrated higher cognitive function. Of the individuals who had mild cognitive impairment or dementia mimic, 6 (0.9%) showed complete cognitive resolution (3 cases) or partial cognitive improvement (3 cases). These 6 cases included two individuals with psychiatric conditions manifesting psychotic features.</p><p><strong>Conclusions: </strong>While rare, reversible psychiatric dementia mimics highlight the importance of comprehensive evaluations in memory clinics, particularly for younger individuals experiencing rapid cognitive decline. The infrequency of reversibility may reflect a strong association between these potentially reversible conditions and dementia risk factors, or their role as prodromes of dementia itself.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251329804"},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric and behavioral symptom clusters in frontotemporal dementia.","authors":"Corinne Sejourne, Megan S Barker, Madison R Heath, Yunglin Gazes, Rachel Fremont, Yedili Genao Perez, Luke J Hearne, Eric M Wassermann, Michael C Tierney, Masood Manoochehri, Edward D Huey, Jordan Grafman","doi":"10.1177/25424823251324391","DOIUrl":"10.1177/25424823251324391","url":null,"abstract":"<p><strong>Background: </strong>Non-Alzheimer's disease dementias, including frontotemporal dementia (FTD) can be difficult to characterize due to the predominance of distinct behavioral and neuropsychiatric symptoms. Widely used measurement tools lack structure and objectivity.</p><p><strong>Objective: </strong>The purpose of this study was to use systematic direct observation of neuropsychiatric and behavioral symptoms, via the Neurobehavioral Rating Scale (NBRS), to characterize clusters of behavioral and neuropsychiatric symptoms in FTD and examine how selected symptom clusters correlate with structural neuroimaging.</p><p><strong>Methods: </strong>We performed a factor analysis on the NBRS data from 172 patients with FTD and examined the neural correlates of the selected symptom clusters in a subsample of 67 patients.</p><p><strong>Results: </strong>Six factors accounted for 56% of total variance across NBRS item scores: Apathy/Blunting, Agitation/Disinhibition, Cognitive/Language, Planning/Insight, Anxiety/Lability, and Psychosis. Symptom clusters showed significant associations with specific regions of cortical thinning: Agitation/Disinhibition with bilateral frontal regions, and Cognition/Language with the left bank of the superior temporal sulcus and supramarginal regions.</p><p><strong>Conclusions: </strong>The selected symptom clusters associated with known regions of atrophy in FTD. The NBRS is an effective observational measure that may extend characterization and understanding of FTD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251324391"},"PeriodicalIF":2.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normative data for the CERAD verbal episodic memory tests in a sample of older illiterate Korean women.","authors":"Hyejin Ahn, Haejung Joung, Min Soo Byun, Jee Eun Park, Gijung Jung, Dahyun Yi, Dong Young Lee","doi":"10.1177/25424823251321750","DOIUrl":"10.1177/25424823251321750","url":null,"abstract":"<p><strong>Background: </strong>Verbal episodic memory tests in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery require literacy. While modified administrations are provided for illiterate individuals, there are no norms for evaluating the performance of illiterate subjects.</p><p><strong>Objective: </strong>Assessing the performance of illiterate individuals has limitations, since existing norms were developed on data from literate populations. The purpose of this study is to provide normative data for illiterate Korean older women.</p><p><strong>Methods: </strong>The participants analyzed in this study were all illiterate. Among a sample of 109 non-demented older adults recruited from community centers for dementia, only 9 were men. Thus, the current analysis developed norms for women. Descriptive statistics were used to summarize participants' characteristics and test scores. Linear regressions were conducted to examine the effect of age on verbal episodic memory tests.</p><p><strong>Results: </strong>Age was found to be significantly associated with performance on all word list tests. Age was divided into two groups based on the average value for sufficient sample size and showed a significant difference in test performance: 60-75, ≥76 years.</p><p><strong>Conclusions: </strong>Evaluating illiterate women using existing standards has the limitation of underestimating their performance relative to their actual skills. The present normative data are expected to enable researchers and clinicians to more accurately evaluate the results of the three verbal episodic memory tests, including the Word List Memory, Word List Recall, and Word List Recognition in older illiterate Korean women.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251321750"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic exposure to a synthetic cannabinoid improves cognition and increases locomotor activity in Tg4-42 Alzheimer's disease mice.","authors":"Frederik W Ott, Marius E Sichler, Caroline Bouter, Marzieh Enayati, Jens Wiltfang, Thomas A Bayer, Nicola Beindorff, Maximilian J Löw, Yvonne Bouter","doi":"10.1177/25424823241306770","DOIUrl":"10.1177/25424823241306770","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and behavior impairments. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease modifying and easily accessible therapies. Emerging evidence suggests that targeting the endocannabinoid system may hold promise for AD therapy as it plays a crucial role in different physiological processes, including learning, memory and anxiety, as well as inflammatory and immune responses.</p><p><strong>Objective: </strong>In this study, we investigated the therapeutic potential of the synthetic cannabinoid WIN 55,212-2 on memory deficits in Tg4-42 transgenic mice.</p><p><strong>Methods: </strong>Tg4-42 mice were assigned to two treatment groups to investigate the preventive effects of WIN 55,212-2 after a prolonged washout period, as well as the therapeutic effects of WIN 55,212-2 on behavior. Furthermore, the effects of WIN 55,212-2 treatment on AD pathology, including inflammation, amyloid-β load, neurogenesis, and brain glucose metabolism, were evaluated.</p><p><strong>Results: </strong>Therapeutic WIN 55,212-2 treatment rescued recognition memory and spatial reference deficits in Tg4-42 mice. Furthermore, therapeutic WIN 55,212-2 administration improved motor performance. In addition, preventative WIN 55,212-2 treatment rescued spatial learning and reference memory deficits. Importantly, WIN 55,212-2 treatment did not affect anxiety-like behavior. However, therapeutic and preventative WIN 55,212-2 treatment resulted in an increase locomotor activity and swimming speed in Tg4-42 mice. WIN-treatment reduced microgliosis in the hippocampus of preventively treated mice and rescued brain glucose metabolism in therapeutically treated Tg4-42 mice.</p><p><strong>Conclusions: </strong>Our findings emphasize the therapeutic promise of the synthetic cannabinoid WIN 55,212-2 in alleviating behavioral and cognitive deficits linked to AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241306770"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How follow-up period in prospective cohort studies affects the relationship between baseline fish consumption and risk of Alzheimer's disease and dementia.","authors":"William B Grant","doi":"10.1177/25424823251324397","DOIUrl":"10.1177/25424823251324397","url":null,"abstract":"<p><strong>Background: </strong>Diet plays an important role in the risk of Alzheimer's disease (AD) and dementia. Adherence to the Mediterranean diet is regarded as one way to reduce risk. Fish is a component of the Mediterranean diet. Participant variables change with time, resulting in \"regression dilution\".</p><p><strong>Objective: </strong>The objective is to investigate the role of follow-up period after measurement of dietary fish intake with risk of AD and dementia.</p><p><strong>Methods: </strong>A recent meta-analysis of prospective cohort studies is used to examine this effect for dietary fish and incidence of dementia and AD.</p><p><strong>Results: </strong>For seven dementia studies with mean follow-up periods from one to ten years, the regression fit to the data is relative risk (RR) = 0.19 + (0.087 × Follow up [years], <i>r </i>= 0.84, adjusted <i>r²</i> = 0.66, <i>p </i>= 0.009). However, when mean age of the participants was added to the analysis, the effect of follow-up period became non-significant. For five AD studies with follow-up periods from 3.9 to 9.8 years, the regression fit to the data is RR = 0.11 + (0.095 × follow up [years]), <i>r </i>= 0.93, adjusted <i>r²</i> = 0.87, <i>p </i>= 0.02). The RR for the regression fit to the shortest follow-up periods are 40% greater for dementia than the standard meta-analysis suggests and 70% greater for AD.</p><p><strong>Conclusions: </strong>Prospective cohort studies of diet and health outcomes should reassess variables every few years. Meta-analyses should consider the effect of mean follow-up periods and mean age of the participants during follow up.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251324397"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of caregiving burden on serum homocysteine and folate levels in spouses of patients with cognitive impairment.","authors":"Ho Yeong Jeong, Shin Young Park, Jeong Lan Kim, Sang Yoon Kim, So Yeon Jeon","doi":"10.1177/25424823251322499","DOIUrl":"10.1177/25424823251322499","url":null,"abstract":"<p><strong>Background: </strong>Spousal caregivers (SCGs) of patients with cognitive impairment are predisposed to an elevated risk of cardiovascular disease and cognitive decline. Homocysteine and folate levels are potential modifiable biomarkers for these risks, given their associations with cardiovascular and cognitive health.</p><p><strong>Objective: </strong>This study aimed to examine the association of the caregiving burden with homocysteine and folate levels in SCGs.</p><p><strong>Methods: </strong>This study included 107 SCGs and their care recipients who visited the Chungnam National University Hospital between May 2020 and May 2023. The caregiving burden was quantified using the Zarit Burden Interview, and blood assays were performed after overnight fasting. We adjusted for the age and sex of SCGs and the clinical diagnosis of care recipients as covariates.</p><p><strong>Results: </strong>The caregiving burden of SCGs showed a significant positive correlation with their homocysteine level (<i>β </i>= 0.219, <i>t </i>= 2.165, <i>p </i>= 0.033). In contrast, caregiving burden and folate showed an inverse correlation (<i>β </i>= -0.207, <i>t </i>= -1.997, <i>p </i>= 0.049). Furthermore, the association between caregiving burden and homocysteine levels remained significant after including vascular risk score and physical activity level as covariates (<i>p </i>= 0.042).</p><p><strong>Conclusions: </strong>Our findings indicate that the caregiving burden of SCGs in individuals with cognitive impairment is associated with elevated homocysteine levels and low folate levels, potentially exacerbating the risk of cardiovascular disease and cognitive decline. These findings underscore the importance of monitoring homocysteine and folate as modifiable biomarkers to address and potentially mitigate health risks in SCGs.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251322499"},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning uncovers novel sex-specific dementia biomarkers linked to autism and eye diseases.","authors":"Ayub Khan, Ali R Ghasemi, Krista K Ingram, Ahmet Ay","doi":"10.1177/25424823251317177","DOIUrl":"10.1177/25424823251317177","url":null,"abstract":"<p><strong>Background: </strong>Recently, microRNAs (miRNAs) have attracted significant interest as predictive biomarkers for various types of dementia, including Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), normal pressure hydrocephalus (NPH), and mild cognitive impairment (MCI). Machine learning (ML) methods enable the integration of miRNAs into highly accurate predictive models of dementia.</p><p><strong>Objective: </strong>To investigate the differential expression of miRNAs across dementia subtypes compared to normal controls (NC) and analyze their enriched biological and disease pathways. Additionally, to evaluate the use of these miRNAs in binary and multiclass ML models for dementia prediction in both overall and sex-specific datasets.</p><p><strong>Methods: </strong>Using data comprising 1685 Japanese individuals (GSE120584 and GSE167559), we performed differential expression analysis to identify miRNAs associated with five dementia groups in both overall and sex-specific datasets. Pathway enrichment analyses were conducted to further analyze these miRNAs. ML classifiers were used to create predictive models of dementia.</p><p><strong>Results: </strong>We identified novel differentially expressed miRNA biomarkers distinguishing NC from five dementia subtypes. Incorporating these miRNAs into ML classifiers resulted in up to a 27% improvement in dementia risk prediction. Pathway analysis highlighted neuronal and eye disease pathways associated with dementia risk. Sex-specific analyses revealed unique biomarkers for males and females, with miR-128-1-5 as a protective factor for males in AD, VaD, and DLB, and miR-4488 as a risk factor for female AD, highlighting distinct pathways and potential therapeutic targets for each sex.</p><p><strong>Conclusions: </strong>Our findings support existing dementia etiology research and introduce new potential and sex-specific miRNA biomarkers.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251317177"},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing peripheral immunocytes of Bacillus Calmette Guerin-vaccinated melanoma patients to reveal preventive Alzheimer's disease mechanisms, possibly via the unfolded protein response.","authors":"Benjamin Y Klein, Inna Ben-David, Ofer N Gofrit, Charles L Greenblatt","doi":"10.1177/25424823241309664","DOIUrl":"10.1177/25424823241309664","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) dysfunctional unfolded protein response (UPR) is revealed by amyloid-β aggregates. Normally, UPR reacts to endoplasmic reticulum stress by resolving misfolded/aggregated proteins, and UPR failure induces brain-cell apoptosis consistent with AD pathology. Peripheral blood mononuclear cells (PBMC) and immunocyte brain infiltrates are involved in AD pathogenesis, whose risk is lowered by the Bacillus Calmette Guerin (BCG) vaccine. Hypothetically, BCG prevents AD caused by UPR-driven apoptosis in PBMC brain infiltrates, corrected by BCG-vaccinated PBMC brain infiltrates.</p><p><strong>Objective: </strong>To reveal whether BCG shifts the UPR towards cell survival. Method: PBMC proteins from 6 individuals were compared by immuno-electrophoresis before and after BCG hypervaccination. Cryopreserved PBMC provided an opportunity to analyze the BCG impact on the UPR, although their donor destiny to develop AD was unknown. UPR signaling responsive to BCG was recorded to examine if BCG can influence UPR signaling and thereby explain the previously demonstrated AD prevention by BCG.</p><p><strong>Results: </strong>UPR signal levels were scored according to positive versus negative cell survival odds by the BCG impact on a dozen UPR signals. The balance between positive and negative scores of individuals emphasizes the impact of the BCG vaccine on the UPR. The antiapoptotic UPR signals under BCG show opposite trends to UPR signals in AD brains, reported by the literature. In conclusion, 3/6 individuals had superior PBMC survival chances under BCG.</p><p><strong>Conclusions: </strong>These results suggest that the UPR is part of the mechanism responsible for reducing the risk of AD, as previously shown among BCG-treated bladder cancer patients.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241309664"},"PeriodicalIF":2.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}