Current Alzheimer research最新文献

{"title":"Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease.","authors":"Kunal Bhattacharya, Dalakamon Sungoh, Daphilari Kharmujai, Ashraful Islam, Dibyajyoti Das, Saurav Kumar Jha, Nongmaithem Randhoni Chanu, Bhaswati Kashyap, Nilutpal Sharma Bora, Bhargab Jyoti Sahariah, Satyendra Deka, Pukar Khanal","doi":"10.2174/0115672050358848241211080546","DOIUrl":"10.2174/0115672050358848241211080546","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of <i>Flemingia vestita (FV)</i> phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.</p><p><strong>Materials and methods: </strong>Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes.</p><p><strong>Results: </strong>8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions.</p><p><strong>Discussion: </strong>The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology.</p><p><strong>Conclusion: </strong>8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"578-598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between Physical Performance Tests with Cognitive Changes: The Moderating Effect of Cognitive Status.","authors":"Zhi Hao Lim, Junhong Yu, Sangita Kuparasundram, Rathi Mahendran, Ted Kheng Siang Ng","doi":"10.2174/0115672050342857241025091918","DOIUrl":"10.2174/0115672050342857241025091918","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within Western populations with a frequent focus on late neurocognitive diagnostic stages (i.e., Alzheimer's disease), reducing their generalizability to the Asian population and early neurocognitive stages. To address these knowledge gaps, our study investigated longitudinal associations between physical performance measures at baseline and cognitive change in global cognition, executive functioning (EF) based and non-executive functioning (non- EF) based cognitive domains within the Singaporean population. The moderating role of early neurocognitive status, namely mild cognitive impairment (MCI) and cognitively normal (CN), was also examined.</p><p><strong>Methods: </strong>This paper examined data from 347 participants (CN = 284; MCI = 63) who participated in the Community Health and Intergenerational (CHI) study at baseline and follow-up. Data from a neurocognitive battery and three physical performance tests, namely the timed-up and go (TUG), fast gait speed (FGS) and 30-second chair-stand test (30s-CST), were analysed using multivariate linear regression models.</p><p><strong>Results: </strong>Only one significant association between FGS scores and cognitive change in Semantic Fluency was observed; other associations were not significant. Cognitive status also significantly moderated associations between TUG/30s-CST tasks with several neurocognitive tests.</p><p><strong>Conclusion: </strong>The lack of significant longitudinal associations between baseline physical performance measures and cognitive change differed from findings in the literature. Nevertheless, the moderating role of cognitive status further highlighted the need to account for cognitive status when exploring such associations within a heterogeneous group of older adults without dementia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"423-436"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the Role of Oligodendrocyte Genes in the Diagnosis of Alzheimer's Disease through Machine Learning and Bioinformatics Analysis.","authors":"Chen Yan, Li Chen, Yao Yinhui, Shang Yazhen","doi":"10.2174/0115672050338777241028071955","DOIUrl":"10.2174/0115672050338777241028071955","url":null,"abstract":"<p><strong>Background: </strong>Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD pathology. When oligodendrocytes are subjected to amyloid-beta (Aβ) toxicity, this damage compromises the structural integrity of myelin and results in a reduction of myelin-associated proteins. Consequently, the impairment of myelin integrity leads to a slowdown or cessation of nerve signal transmission, ultimately contributing to cognitive dysfunction and the progression of AD. Consequently, elucidating the relationship between oligodendrocytes and AD from the perspective of oligodendrocytes is instrumental in advancing our understanding of the pathogenesis of AD.</p><p><strong>Objective: </strong>Here, an attempt is made in this study to identify oligodendrocyte-related biomarkers of AD.</p><p><strong>Methods: </strong>AD datasets were obtained from the Gene Expression Omnibus database and used for consensus clustering to identify subclasses. Hub genes were identified through differentially expressed genes (DEGs) analysis and oligodendrocyte gene set enrichment. Immune infiltration analysis was conducted using the CIBERSORT method. Signature genes were identified using machine learning algorithms and logistic regression. A diagnostic nomogram for predicting AD was developed and validated using external datasets and an AD model. A small molecular compound was identified using the eXtreme Sum algorithm.</p><p><strong>Results: </strong>46 genes were found to be significantly correlated with AD progression by examining the overlap between DEGs and oligodendrocyte genes. Two subclasses of AD, Cluster A, and Cluster B, were identified, and 9 signature genes were identified using a machine learning algorithm to construct a nomogram. Enrichment analysis showed that 9 genes are involved in apoptosis and neuronal development. Immune infiltration analysis found differences in immune cell presence between AD patients and controls. External datasets and RT-qPCR verification showed variation in signature genes between AD patients and controls. Five small molecular compounds were predicted.</p><p><strong>Conclusion: </strong>It was found that 9 oligodendrocyte genes can be used to create a diagnostic tool for AD, which could help in developing new treatments.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"437-455"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Long-term Partner Observation in Cognitive Evaluation: A Very Early Creutzfeldt-Jakob Disease in a Patient with Mild Cognitive Impairment.","authors":"Hatice Yuksel, Elif Bademci Eren, Baris Maldar, Ayse Pinar Titiz","doi":"10.2174/0115672050309694240708052535","DOIUrl":"10.2174/0115672050309694240708052535","url":null,"abstract":"<p><strong>Background: </strong>Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.</p><p><strong>Case presentation: </strong>A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.</p><p><strong>Conclusion: </strong>Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"214-218"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Effects of Arctiin on Alzheimer's Disease-like Model in Rats by Reducing Oxidative Stress, Inflammasomes and Fibrosis.","authors":"Mohamed T Almeaqli, Yazeed Alaidaa, Faisal M Alnajjar, Abdullah S Al Shararh, Danah S Alharbi, Yazeed I Almslmani, Yousef A Alotibi, Hani S Alrashidi, Wael A Alshehri, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050333388240801043509","DOIUrl":"10.2174/0115672050333388240801043509","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.</p><p><strong>Objectives: </strong>We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Methods: </strong>AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Results: </strong>In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Conclusion: </strong>Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"276-288"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1 and Prolactin.","authors":"Yeşim Olğun, Cana Aksoy Poyraz, Melda Bozluolçay, Dildar Konukoğlu, Burç Çağrı Poyraz","doi":"10.2174/0115672050313419240520051751","DOIUrl":"10.2174/0115672050313419240520051751","url":null,"abstract":"<p><strong>Background: </strong>Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.</p><p><strong>Objective: </strong>This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.</p><p><strong>Methods: </strong>Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.</p><p><strong>Results: </strong>Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.</p><p><strong>Conclusion: </strong>The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"109-119"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Alzheimer's Digital Caregiving through Large Language Models.","authors":"Sujin Kim, Dong Y Han, Jihye Bae","doi":"10.2174/0115672050301740241118044604","DOIUrl":"10.2174/0115672050301740241118044604","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's Disease and Related Dementias (AD/ADRD) present significant caregiving challenges, with increasing burdens on informal caregivers. This study examines the potential of AI-driven Large Language Models (LLMs) in developing digital caregiving strategies for AD/ADRD. The objectives include analyzing existing caregiving education materials (CEMs) and mobile application descriptions (MADs) and aligning key caregiving tasks with digital functions across different stages of disease progression.</p><p><strong>Methods: </strong>We analyzed 38 CEMs from the National Library of Medicine's MedlinePlus, along with associated hyperlinked web resources, and 57 MADs focused on AD digital caregiving. Using ChatGPT 3.5, essential caregiving tasks were extracted and matched with digital functionalities suitable for each stage of AD progression, while also highlighting digital literacy requirements for caregivers.</p><p><strong>Results: </strong>The analysis categorizes AD caregiving into 4 stages-Pre-Clinical, Mild, Moderate, and Severe-identifying key tasks, such as behavior monitoring, daily assistance, direct supervision, and ensuring a safe environment. These tasks were supported by digital aids, including memory- enhancing apps, Global Positioning System (GPS) tracking, voice-controlled devices, and advanced GPS tracking for comprehensive care. Additionally, 6 essential digital literacy skills for AD/ADRD caregiving were identified: basic digital skills, communication, information management, safety and privacy, healthcare knowledge, and caregiver coordination, highlighting the need for tailored training.</p><p><strong>Conclusion: </strong>The findings advocate for an LLM-driven strategy in designing digital caregiving interventions, particularly emphasizing a novel paradigm in AD/ADRD support, offering adaptive assistance that evolves with caregivers' needs, thereby enhancing their shared decision-making and patient care capabilities.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"503-516"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trafficking of Muscarinic 1 Acetylcholine Receptor Regulated by VPS35 in Alzheimer's Disease.","authors":"Chen Wang, Xi Chen, Zhenzhen Yu","doi":"10.2174/0115672050356990250111200217","DOIUrl":"10.2174/0115672050356990250111200217","url":null,"abstract":"<p><strong>Introduction: </strong>Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the Gprotein- coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).</p><p><strong>Aims: </strong>Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.</p><p><strong>Methods: </strong>The interaction between VPS35 and M1AChR was studied by co-immunoprecipitation method, and the recycling of M1AChR influence by VPS35 was analyzed using biotinylation technology.</p><p><strong>Results: </strong>It was found that VPS35 affected the localization of M1AChR on the cell membrane by regulating intracellular M1AChR transport, thus controlling the M1AChR-mediated cholinergic signaling pathway.</p><p><strong>Conclusion: </strong>The findings presented here provide a potential pathogenesis and pathway for the treatment of AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"735-744"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Alzheimer's Disease Biomarkers.","authors":"Kuan Li, Yujie Gao, Muxi Liu, Yizhao Chen","doi":"10.2174/0115672050366767241223050957","DOIUrl":"10.2174/0115672050366767241223050957","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual onset and complex pathological mechanisms. Clinically, it presents with progressive cognitive decline and behavioral impairments, making it one of the most common causes of dementia. The intricacies of its pathogenesis are not fully understood, and current treatment options are limited, with diagnosis typically occurring at intermediate to advanced stages. The development of new biomarkers offers a crucial avenue for the early diagnosis of AD and improving patient outcomes. Several biomarkers with high specificity have been identified. This article reviews biomarkers related to tau protein, β-amyloid, and blood cells to deepen our understanding of AD and emphasize the advantages and disadvantages of various biomarkers in order to explore further and mine new biomarkers for AD diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"791-803"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Metabolomics Findings and Brain Hypometabolism in Mild Cognitive Impairment and Alzheimer's Disease.","authors":"Moein Mir, Parinaz Khosravani, Elham Ramezannezhad, Fatemeh Pourali Saadabad, Marjan Falahati, Mahsa Ghanbarian, Parsa Saberian, Mohammad Sadeghi, Nafise Niknam, Sanaz Eskandari Ghejelou, Masoumeh Jafari, David Gulisashvili, Mahsa Mayeli","doi":"10.2174/0115672050350196250110092338","DOIUrl":"10.2174/0115672050350196250110092338","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disease with rising prevalence due to the aging global population. Existing methods for diagnosing AD are struggling to detect the condition in its earliest and most treatable stages. One early indicator of AD is a substantial decrease in the brain's glucose metabolism. Metabolomics can detect disturbances in biofluids, which may be advantageous for early detection of some AD-related changes. The study aims to predict brain hypometabolism in Alzheimer's disease using metabolomics findings and develop a predictive model based on metabolomic data.</p><p><strong>Methods: </strong>The data used in this study were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. We conducted a longitudinal study with three assessment time points to investigate the predictive power of baseline metabolomics for modeling longitudinal fluorodeoxyglucose- positron emission tomography (FDG-PET) trajectory changes in AD patients. A total of 44 participants with AD were included. The Alzheimer's Disease Assessment Scale (ADAS), the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) were used for cognitive assessments. A single global brain hypo-metabolism index was used as the outcome variable.</p><p><strong>Results: </strong>Across models, we observed consistent positive relationships between specific cholesterol esters - CE (20:3) (p = 0.005) and CE (18:3) (p = 0.0039) - and FDG-PET metrics, indicating these baseline metabolites may be valuable indicators of future PET score changes. Selected triglycerides like DG-O (16:0-20:4) also showed time-specific positive associations (p = 0.017).</p><p><strong>Conclusion: </strong>This research provides new insights into the disruptions in the metabolic network linked to AD pathology. These findings could pave the way for identifying novel biomarkers and potential treatment targets for AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"679-689"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}