Journal of Alzheimer's disease reports最新文献

{"title":"Novel donepezil-tacrine hybrid (TAHB3) induces neurodifferentiation, neuroprotective effects, and activates the PI3K/AKT pathway on PC12 cells.","authors":"Renata Melo Dos Santos Ono, Natália Chermont Dos Santos Moreira, Ivone Carvalho, Geraldo Aleixo Passos, Elza Tiemi Sakamoto-Hojo","doi":"10.1177/25424823241309268","DOIUrl":"10.1177/25424823241309268","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease characterized by the impairment of cognitive functions and neuronal loss. AD has no cure; current treatments like acetylcholinesterase inhibitors (AChEI) alleviate symptoms but do not halt disease progression.</p><p><strong>Objective: </strong>We aimed to evaluate the effects and mechanisms of two novel AChEI hybrid compounds (TAHB3 and TA8Amino), regarding cytotoxicity, neuroprotection and neurodifferentiation in PC12 cells.</p><p><strong>Methods: </strong>The effects of TAHB3 and TA8Amino on neurodifferentiation were analyzed on PC12 cells which were treated with AChEI compounds for seven days, following morphological, and quantitative analyses to calculate the differentiation percentages, neurite length, and protein expression. Regarding cytotoxicity and neuroprotection assays, PC12 cells were differentiated into mature neurons, then treated with TAHB3 or TA8Amino, following a posttreatment with H₂O₂ (an inducer of oxidative damage); the analyses were performed using the XTT assay and flow cytometry.</p><p><strong>Results: </strong>The hybrid compound TAHB3 induced differentiation of PC12 cells, but TA8Amino did not cause the same effect. Both compounds did not show cytotoxic effects to PC12 cells and did not change the cell cycle progression, nor induce cell death. Only TAHB3 showed neuroprotective potential against induced-oxidative damage, and TAHB3 increased the levels of p-AKT, suggesting its action through the activation of the PI3K/AKT pathway.</p><p><strong>Conclusions: </strong>Our results showed that TAHB3 can induce neurodifferentiation, besides a neuroprotective activity, indicating the potential of AChEI hybrid compounds as novel candidates to be explored for the establishment of novel therapeutic strategies for patients with AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241309268"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544848","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":"Lower expression of <i>BIN1's</i> neuronal isoform in vulnerable excitatory neurons increases risk in Alzheimer's disease.","authors":"Rajesh Ranganathan, Siwen Li, Georgy Sapozhnikov, Shoutang Wang, You-Qiang Song","doi":"10.1177/25424823241296018","DOIUrl":"10.1177/25424823241296018","url":null,"abstract":"<p><strong>Background: </strong>Neurons in Alzheimer's disease (AD) experience elevated DNA damage, with DNA repair sites enriched at enhancer regions of genes essential for neuronal survival. Excitatory neurons in the cortical superficial layers expressing <i>CUX2</i> and <i>RORB</i> (Cux2+/Rorb+), are selectively vulnerable in AD, but their relationship to single nucleotide polymorphisms (SNPs) in AD genome-wide association studies (GWAS) is unclear.</p><p><strong>Objective: </strong>This study aimed to identify and characterize functional AD-GWAS SNPs using single-nucleus RNA sequencing data, focusing on selectively vulnerable neurons and DNA repair hotspots.</p><p><strong>Methods: </strong>Filters were applied to identify candidate SNPs based on overlap with repair hotspots, RNA expression, transcription factor binding, AD association, and epigenetic significance. In vitro assays and analyses of large datasets from bulk RNA-seq (n = 1894), proteomics (n = 400), and single-nucleus RNA-seq (n = 424, 1.6 M cells) were conducted.</p><p><strong>Results: </strong><i>BIN1</i> SNP, rs78710909, met multiple criteria - located in an AD-GWAS locus, repair hotspot, and promoter region. rs78710909C exhibits 1.52× higher AD risk and 5.4× differential transcription factor binding. In vitro, rs78710909C shows greater enhancer activity and weaker p53 but stronger E2F1 binding. <i>BIN1</i>'s neuronal isoform is neuroprotective, but its AD expression is lower (p < 0.01). Moreover, only in AD and Cux2+/Rorb + neurons, rs78710909C is associated with a lower average <i>BIN1</i> neuronal isoform ratio (p < 0.01). The genes upregulated in neurons with lower neuronal isoform ratio were associated with the hallmarks of AD pathology.</p><p><strong>Conclusions: </strong>In a disease-relevant mechanism, the <i>BIN1</i> SNP rs78710909C is associated with a lower ratio of <i>BIN1</i>'s neuronal isoform which increases the vulnerability of specific excitatory neurons in AD patients.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241296018"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544841","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":"Sleepiness, sleep time, and depression of caregivers are linked with sleep and behaviors of their paired partners with dementia.","authors":"Carol A Manning, Anna Youngkin, Mark Quigg","doi":"10.1177/25424823241300981","DOIUrl":"10.1177/25424823241300981","url":null,"abstract":"<p><strong>Background: </strong>Sleep difficulties in people with Alzheimer's disease (AD) and their caregivers (CGs) have been documented. Additionally, sleep disturbances are a risk for AD indicating that poor sleep in CGs may place them at risk for AD. Little is known about the relationship between sleep in people with dementia (PWD) and their CGs.</p><p><strong>Objective: </strong>This pilot study examines sleep in PWD and CGs dyads, and the relationship between PWD sleep and CG sleep, cognition, and burden. We explore whether disordered sleep, degree of dementia and PWD behaviors are related to CG sleep difficulties and burden.</p><p><strong>Methods: </strong>We examined sleep using overnight polysomnography (PSG) and day/night activity using 14-day actigraphy in PWD/CG dyads form the Virginia Alzheimer's Disease Center Clinical Cohort. Dyad members received the Montreal Cognitive Assessment (MoCA), behavioral and mood assessments. CGs completed CG burden and preparedness assessments.</p><p><strong>Results: </strong>Mean activity from actigraphy did not differ within dyad members. PSG measurement of total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SEff), and wake after sleep onset (WASO) revealed that CGs had significantly decreased TST compared to their PWD and experienced greater SOL. Lower PWD MoCA scores were unrelated to CG sleep. However, PWD neuropsychiatric symptoms and CG burden correlated with worse CG SOL.</p><p><strong>Conclusions: </strong>Our findings suggest that chronic rest and activity are linked within dyad members and that when separated, CGs experience shorter TST, lower SEff, and longer SOL than their partners. Additionally neuropsychiatric symptoms and CG burden were associated with worse CG sleep.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241300981"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544927","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":"Neuropsychological and clinical indicators of Lewy body and Alzheimer's pathology.","authors":"Austin J Simpson, Kathryn A Wyman-Chick, Michael S Daniel","doi":"10.1177/25424823241304386","DOIUrl":"10.1177/25424823241304386","url":null,"abstract":"<p><strong>Background: </strong>Clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) poses significant challenges due to pathological comorbidity. Similar ages of onset and overlapping cognitive and psychiatric symptoms can lead to diagnostic inaccuracy and inappropriate treatment recommendations.</p><p><strong>Objective: </strong>Identify the best combination of clinical and neuropsychological predictors of AD, DLB, and mixed DLB/AD neuropathology in dementia patients.</p><p><strong>Methods: </strong>Using the National Alzheimer's Coordinating Center dataset, we selected either pure AD (<i>n = </i>189), DLB (<i>n </i>= 21), or mixed DLB/AD (<i>n </i>= 42) patients on autopsy. Neuropsychological and clinical predictors, including core clinical features of DLB, were entered into multivariable logistic regressions.</p><p><strong>Results: </strong>Gait disturbances (odds ratio (OR) = 19.32; p = 0.01), visual-spatial complaints (OR = 6.06; p = 0.03), and visual hallucinations (OR = 31.06; p = 0.002) predicted DLB compared to AD, along with better memory (OR = 3.42; p = 0.003), naming (OR = 3.35; p = 0.002), and worse processing speed (OR = 0.51; p = 0.01). When comparing DLB to DLB/AD, gait disturbances (OR = 6.33; p = 0.01), increased depressive symptoms (OR = 1.44; p = 0.03), and better memory (OR = 3.01; p = 0.004) predicted DLB. Finally, rapid eye movement sleep behavior disorder (RBD) (OR = 6.44; p = 0.004), parkinsonism severity (OR = 1.07; p = 0.02), and lower depressive symptoms (OR = 0.70; p = 0.006) and memory impairment (OR = 0.57; p = 0.02) distinguished DLB/AD from AD.</p><p><strong>Conclusions: </strong>Our study converges with prior research suggesting specific neuropsychological and clinical features can help distinguish DLB from AD. Neuropsychological differentiation becomes more challenging among mixed pathologies and in advanced cognitive impairment, although the presence of RBD and parkinsonism distinguished DLB. Earlier clinical assessment and incorporation of in vivo and postmortem biomarkers should enhance diagnostic accuracy and understanding of disease characteristics, offering significant relevance for disease-modifying treatments.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241304386"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544845","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":"Alzheimer's disease classification by supervised and intelligent techniques.","authors":"Jabli Mohamed Amine, Moussa Mourad","doi":"10.1177/25424823241311838","DOIUrl":"10.1177/25424823241311838","url":null,"abstract":"<p><strong>Background: </strong>Significant advancements in neuroimaging have emerged over the past decade, notably through positron emission tomography (PET) and magnetic resonance imaging (MRI) for diagnosing Alzheimer's disease (AD) and its precursor, mild cognitive impairment (MCI). Combining imaging modalities with machine learning (ML) techniques enhances diagnostic accuracy.</p><p><strong>Objective: </strong>To develop predictive models using pre-treatment brain imaging data to distinguish between normal controls (NC), MCI, and AD stages, improving diagnostic precision.</p><p><strong>Methods: </strong>We utilized the Alzheimer's Disease Neuroimaging Initiative database, processing 3D MRI, PET Florbetaben, and PET Flortaucipir images. Techniques included convolutional neural networks (CNN), fuzzy logic, and multi-layer perceptron (MLP). Feature extraction involved amyloid-β volume, tau protein levels, and empty space volumes.</p><p><strong>Results: </strong>The fuzzy logic approach achieved a classification accuracy of 99.1%, outperforming CNN (90.67%) and MLP (94%). Integration of multimodal data significantly enhanced performance compared to single-modality approaches.</p><p><strong>Conclusions: </strong>Our study demonstrates that integrating advanced ML techniques with multimodal neuroimaging can effectively classify AD stages. These findings address critical gaps in early detection and provide a foundation for future clinical applications.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241311838"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544258","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":"Heat shock protein 70 in Alzheimer's disease and other dementias: A possible alternative therapeutic.","authors":"Antonio Valle-Medina, Claudia Camelia Calzada-Mendoza, María Esther Ocharan-Hernández, Carlos Alberto Jiménez-Zamarripa, Teresa Juárez-Cedillo","doi":"10.1177/25424823241307021","DOIUrl":"10.1177/25424823241307021","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is considered a global health issue with a high social burden due to the level of disability it causes in those who suffer from it. In the absence of a therapeutic alternative for this disease, we will follow one of the biochemical pathways involved in the development of AD, which is related to molecular chaperones. The molecules are responsible for eliminating toxins and misfolded proteins at the cerebral level. These chaperones are a set of proteins from the heat shock proteins (HSPs) family, which, among their functions, help maintain homeostasis and protect cells against stress. Various authors have described the activity of HSPs in different neurodegenerative diseases, highlighting the activity of heat shock protein 70 (HSP70) in the presence of aberrant proteins characteristic of neurodegeneration, such as amyloid-β (Aβ) and tau. The role of HSP70 in AD and other dementias lies in its mechanism, which, along with other proteins from the HSP family, has the capacity to eliminate Aβ aggregates by promoting catalytic pathways. In this review, we explore the biological role of the HSP70 protein in AD and other dementias and its potential therapeutic use.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241307021"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544893","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":"Nomogram for predicting nutritional risk of cognitive impairment.","authors":"Yuhang Chen, Junlin Diao, Xuezhuang Ren, Chunxiang Wei, Xue Zhou","doi":"10.1177/25424823241309262","DOIUrl":"10.1177/25424823241309262","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment patients are prone to malnutrition, which further promotes cognitive decline. Cognitive impairment patients are unable to accurately answer subjective questions in the nutrition screening scale. Therefore, it is crucial to establish a nutritional risk prediction model using objective evaluation indicators to evaluate the nutritional status of cognitive impairment patients during hospitalization.</p><p><strong>Objective: </strong>To develop a nomogram for prediction of the nutritional risk in cognitive impairment patients.</p><p><strong>Methods: </strong>The least absolute shrinkage and selection operator (LASSO) was used for regression analysis, and predictive factors were selected based on 10-fold cross validation. Then, using the selected predictive factors, multivariable logistic regression analysis was performed to obtain the final clinical prediction model. Moreover, the performance of the model was evaluated from receiver operating characteristic curve, calibration curve, and decision curve analysis. Further assessment was conducted through internal validation.</p><p><strong>Results: </strong>Six predictive factors were selected from 20 variables through LASSO, including body mass index, age, triglyceride, taking cognitive-improving drugs, controlling nutritional status, and geriatric nutritional risk index. The area under the receiver operating characteristic curve of the training cohort was 0.91, while the validation cohort was 0.88, indicating that the model constructed with 6 predictors had moderate predictive ability. The decision curve analysis showed that the threshold range for both groups was 0.00-0.80, with the highest net benefit 0.76 for training cohort, while 0.77 for validation cohort.</p><p><strong>Conclusions: </strong>Introducing six predictive factors, the risk nomogram is useful for predicting nutritional risk of cognitive impairment.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241309262"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544846","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":"An experimental framework for conjoint measures of olfaction, navigation, and motion as pre-clinical biomarkers of Alzheimer's disease.","authors":"Katarina Biljman, Illana Gozes, Jacqueline Ck Lam, Victor Ok Li","doi":"10.1177/25424823241307617","DOIUrl":"10.1177/25424823241307617","url":null,"abstract":"<p><p>Elucidating Alzheimer's disease (AD) prodromal symptoms can resolve the outstanding challenge of early diagnosis. Based on intrinsically related substrates of olfaction and spatial navigation, we propose a novel experimental framework for their conjoint study. Artificial intelligence-driven multimodal study combining self-collected olfactory and motion data with available big clinical datasets can potentially promote high-precision early clinical screenings to facilitate timely interventions targeting neurodegenerative progression.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1722-1744"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544219","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":"Deep brain stimulation versus nonsurgical treatment for severe Alzheimer's disease: A long-term retrospective cohort study.","authors":"Junpeng Xu, Bin Liu, Zhebin Feng, Xinguang Yu, Guosong Shang, Yang Liu, Yuxiang Sun, Haonan Yang, Yuhan Chen, Yanyang Zhang, Zhiqi Mao","doi":"10.1177/25424823241297852","DOIUrl":"10.1177/25424823241297852","url":null,"abstract":"<p><strong>Background: </strong>Severe Alzheimer's disease (AD) is characterized by significant neuropsychiatric symptoms and sleep disorders, with limited effectiveness of conservative drug treatments. Deep brain stimulation (DBS) offers a potential alternative.</p><p><strong>Objective: </strong>To evaluate the efficacy, safety, and long-term outcomes of DBS versus conservative treatment in patients with severe AD.</p><p><strong>Methods: </strong>We retrospectively analyzed 40 patients with severe AD diagnosed at the People's Liberation Army General Hospital from 2015 to 2022. Twenty patients received DBS, and twenty received conservative treatment. Treatment effects were assessed using standardized scales at three- and twelve-months post-treatment. Primary outcomes included changes in cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Rating Scale-Cognitive subscale, Clinical Dementia Rating). Secondary outcomes included quality of life, sleep quality, neuropsychiatric symptoms, and caregiver burden (Barthel Index, Functional Activity Questionnaire, Functional Independence Measure (FIM), Neuropsychiatric Inventory (NPI), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PDQI), Zarit Burden Interview (ZBI)].</p><p><strong>Results: </strong>DBS patients showed significantly greater improvements in MMSE, MoCA, FIM, and ZBI scores than controls, suggesting improved cognitive function and quality of life, and reduced caregiver burden (p < 0.05). Notably, DBS significantly reduced HAM-A, HAM-D, and PSQI scores, and improved NPI scores more than controls, indicating significant amelioration of neuropsychiatric symptoms and sleep disorders (p < 0.05).</p><p><strong>Conclusions: </strong>DBS is a safe and reversible treatment that potentially enhances cognitive function and quality of life in severe AD patients and alleviates caregiver burden. For the first time, we report that DBS also improves neuropsychiatric symptoms and sleep disorders, highlighting its clinical potential in AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1677-1689"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544867","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":"Blood RNA transcripts show changes in inflammation and lipid metabolism in Alzheimer's disease and mitochondrial function in mild cognitive impairment.","authors":"Jun-Ichi Iga, Yuta Yoshino, Tomoki Ozaki, Ayumi Tachibana, Hiroshi Kumon, Yu Funahashi, Hiroaki Mori, Mariko Ueno, Yuki Ozaki, Kiyohiro Yamazaki, Shinichiro Ochi, Masakatsu Yamashita, Shu-Ichi Ueno","doi":"10.1177/25424823241307878","DOIUrl":"10.1177/25424823241307878","url":null,"abstract":"<p><strong>Background: </strong>Abnormal immunity in the periphery has been reported in the pathogenesis of Alzheimer's disease (AD).</p><p><strong>Objective: </strong>In this study, blood transcriptome analyses of patients with AD, those with mild cognitive impairment (MCI) due to AD, and heathy controls were performed to elucidate immune-related pathophysiology.</p><p><strong>Methods: </strong>The sample included 63 participants from a complete enumeration study of elderly people in Nakayama town (the Nakayama Study), who were over 65 years of age, diagnosed as (1) healthy controls (N = 21, mean age: 83.8 years), (2) having MCI due to AD (N = 20, mean age: 82.6 years), or (3) having AD (N = 21, mean age: 84.2 years). Every participant underwent blood tests, magnetic resonance imaging, and questionnaires about lifestyle and cognitive function. With transcriptome analysis, differential gene expressions in the blood of the three groups were evaluated by gene ontology, pathway enrichment, and ingenuity pathway analyses, and quantitative real-time PCR was performed.</p><p><strong>Results: </strong>Neutrophil extracellular trap signaling was increased, and lipid metabolism (FXR/RXR activation, triacylglycerol degradation) was decreased in AD, whereas MCI showed protective responses via decreased neutrophil extracellular trap signaling and mitochondrial functions such as upregulation of the sirtuin pathway and downregulation of oxidative stress.</p><p><strong>Conclusions: </strong>Based on these findings and consistent with other published studies, immune cells appear to have important roles in the pathogenesis of AD, and the transcriptome in blood may be useful as a biomarker for diagnosis via monitoring immunity in MCI and AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1690-1703"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544826","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}