Current Alzheimer research最新文献

{"title":"Psychotropic Polypharmacy in Alzheimer's Disease: A Potentially Inappropriate Medication Perspective in Older Adults.","authors":"Kang-Jinyuan Gou, Yuhao Chen, Zehu Sheng, Weihua Yu, Lanyang Wang, Yang Lü","doi":"10.2174/0115672050502495260812063626","DOIUrl":"https://doi.org/10.2174/0115672050502495260812063626","url":null,"abstract":"<p><p>Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD). Consequently, potentially inappropriate medication (PIM) use is particularly common among older adults with AD. Psychotropic polypharmacy may increase the risk of various adverse outcomes beyond cognitive decline. Although geriatric prescribing criteria and dementia-care guidelines offer important safety recommendations, a clinically integrated framework for potentially inappropriate psychotropic medication use in older adults with AD remains insufficiently developed. This article is a narrative review rather than a systematic review or meta-analysis. The authors searched the literature in PubMed, Embase, and the Cochrane Library, focusing on studies, guidelines, consensus statements, regulatory safety warnings, and medication-safety criteria published between January 2015 and June 2026. This review specifically examines anticholinergic drugs, antipsychotics, benzodiazepines and Z-drugs, tricyclic antidepressants, and select newer antidepressants-including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, trazodone, and paroxetine-guided by the 2023 American Geriatrics Society (AGS) Beers Criteria®. Current evidence indicates that these medications may contribute to cognitive decline through anticholinergic burden, sedation, and pharmacodynamic interactions with cholinesterase inhibitors, such as donepezil and memantine. However, the strength of evidence varies considerably across drug classes and study designs, ranging from randomized controlled trials to observational studies and expert consensus. This study also summarizes current nonpharmacological strategies and proposes a structured clinical medication review framework. Overall, this review highlights the importance of minimizing inappropriate psychotropic use in AD, prioritizing non-pharmacological interventions, and conducting individualized risk-benefit assessments in clinical practice.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908602","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":"Structural and Ultrastructural Neuropathological Changes in Alzheimer's Disease: Biomarkers, Current Insights and Emerging Perspectives.","authors":"Sreenivasulu Sura, Emmanuel Oshiogwe Okwuofu, Sowmya Ramakrishnappa, Saravanan Jagadeesan, Siti Saleha Binti Masrudin, Mohamad Aris Mohd Moklas, Krishna Chaitanya Reddy Dandala, John Paul Judson, Nurul Huda Mohd Nor","doi":"10.2174/0115672050468141260805043246","DOIUrl":"https://doi.org/10.2174/0115672050468141260805043246","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) involves progressive brain changes at both the structural and ultrastructural levels, which begin long before patients present with clinical symptoms. These changes relate to the complex processes of amyloid-β deposition, tau accumulation, synaptic damage, glial activation, impaired vascular function, and disruption of large-scale brain networks. Understanding these neurobiological changes is essential for improving diagnosis, biomarker development, and targeted therapy. We conducted a search across PubMed, Scopus, and Web of Science using the terms \"Alzheimer's disease,\" \"brain structure,\" \"ultrastructure,\" \"cryo-electron microscopy,\" and \"neuroimaging.\" We limited our review to peer-reviewed papers published in English. Recent developments in cryo-electron microscopy, super-resolution imaging, in situ cryo-electron tomography, and correlative microscopy have revealed the molecular and subcellular features of amyloid plaques and tau filaments, as well as the associated cellular pathology of AD. These investigations refine current pathophysiological models and improve understanding of molecular-level changes in the brain. Improvements in structural and molecular imaging provide potential new biomarkers and therapeutic targets in AD. Advances in imaging and structural neuroscience could support earlier disease detection and improve clinical outcomes. These advances are helping to connect molecular pathology with structural brain remodelling and may support more precise biomarker interpretation and therapeutic development.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868740","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 Relationship Between Biomarkers in Blood and Urine and Alzheimer's Disease and Sleep Disorders (Long Sleep): A Mendelian Randomization Study.","authors":"Jianran Ma, Zhen Wei, Chunshu Rong, Wei He, Xu Wang, Dexi Zhao","doi":"10.2174/0115672050466562260804080255","DOIUrl":"https://doi.org/10.2174/0115672050466562260804080255","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is a neurological condition that increases in severity from a gradual start. Previous studies have found an association between long sleep (LS) and AD. To slow its progression, it is important to recognize biomarkers associated with the early stages of both AD and LS.</p><p><strong>Methods: </strong>This study aimed to use two-sample Mendelian Randomization (MR) to identify blood and urine biomarkers associated with AD and LS. Thirty-five biomarkers from blood and urine were included as exposures in the MR analysis, while AD and LS were considered the outcomes. The AD dataset included 39,106 patients and 46,828 controls from Europe. Data on sleep duration were obtained from a GWAS in 34,184 cases and 305,742 controls of European ancestry. This study included 35 blood and urine biomarkers across 355,891 participants, including 318,953 white British, 23,582 non-white British, 6,019 African, and 7,338 South Asian participants from the UK Biobank.</p><p><strong>Results: </strong>Cystatin C, CRP, and Non-Albumin protein showed genetic association with AD and LS. The genetic association results after Bonferroni's correction are significant for Non-Albumin Protein in AD and LS.</p><p><strong>Discussion: </strong>This study provides further insight into the genetic associations and relationships among AD, LS, and other biomarkers; it also presents several potential candidates for AD and LS diagnosis and treatment. The opposing roles of C-reactive Protein, Cystatin C, and Non-Albumin protein in AD and LS warrant a greater exploration of their differential functions at various ages and in specific brain microenvironments in future studies.</p><p><strong>Conclusion: </strong>This study provides a theoretical basis for the diagnosis and treatment of AD and LS. More experiments are needed in the future to verify this prediction.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868745","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":"Regional Fractal Dimension as a Complementary Morphometric Marker in Alzheimer's Disease.","authors":"Yongha Gi, Hyeongjin Lim, A Hyun Jung, Jeongwon Lee, Sangyoon Park, Seol-Hee Baek, Jong Hyun Kim, Byung-Jo Kim, Myonggeun Yoon","doi":"10.2174/0115672050509238260717071733","DOIUrl":"https://doi.org/10.2174/0115672050509238260717071733","url":null,"abstract":"<p><strong>Introduction: </strong>Fractal Dimension (FD) has been proposed as a marker of structural complexity in Alzheimer's Disease (AD), but its regional distribution and complementary value beyond conventional morphometry remain unclear. This study investigated whether regional FD captures AD-related structural alterations distinct from regional volume and thickness.</p><p><strong>Methods: </strong>Using T1-weighted MRI from ADNI1, with external validation in MIRIAD and NACC, we extracted 79 cortical, subcortical, and CSF-related regions and computed volume, thickness, and FD for each region. We assessed covariate-adjusted disease-stage associations, residual FD after linear and nonlinear adjustment for morphometric and demographic factors, clinical associations, and classification performance using conventional features, FD alone, or their combination.</p><p><strong>Results: </strong>FD showed localized, region-dependent alterations, particularly in the hippocampus, ventricular structures, and caudate. In linear residual analysis, FD associations remained strongest in the bilateral inferior lateral ventricles and left caudate after morphometric and demographic adjustment. Nonlinear adjustment attenuated the ventricular associations, suggesting sensitivity to nonlinear size-shape effects, whereas the left caudate remained consistently associated with diagnostic stage. Adjusted FD also showed modest but significant associations with clinical measures. Combining FD with volume and thickness showed modest additive classification utility.</p><p><strong>Discussion: </strong>Regional FD captures selected aspects of structural complexity that are not fully represented by volume or thickness under the tested framework. Ventricular FD appears sensitive to nonlinear size-shape effects, whereas caudate FD may provide more stable residual information.</p><p><strong>Conclusion: </strong>Regional FD provides complementary, region-dependent morphometric information in AD and should be interpreted as an additive descriptor rather than a standalone biomarker.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809746","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":"Dynamic Entropic Mapping of Alzheimer's Neuropathology: Eyes-Open and Eyes-Closed EEG Biomarkers through Wavelet Entropy Analysis.","authors":"Yujiao Tong, Guanqun Hu, Lingfeng Liu, Ying Zhang, Nan Jiang, Ying Hou, Meiyun Zhang","doi":"10.2174/0115672050450560260119050625","DOIUrl":"https://doi.org/10.2174/0115672050450560260119050625","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is characterized by amyloid-β plaques and tau tangles, while current diagnostic tools are often invasive and costly. Electroencephalography (EEG) offers a non-invasive alternative, with alpha rhythm abnormalities as key features. Impaired alpha reactivity during the transition from Eyes-Closed (EC) to Eyes-Open (EO) reflects early thalamocortical dysfunction.</p><p><strong>Objective: </strong>This study employs EO/EC wavelet entropy analysis to assess neurodynamic features across frequency bands, aiming to explore entropy-based EEG markers for early AD detection.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 60 participants (30 AD and 30 controls). EEG was recorded during 60-second EC and Eyes-Open (EO) states using a 20-channel system. Continuous Wavelet Transform (CWT) and multiscale entropy were used to assess complexity differences across bands and regions between groups.</p><p><strong>Results: </strong>AD patients showed reduced alpha entropy differences between EC and EO states. Multiscale entropy difference (ΔEN α ) analysis revealed weaker modulation in β-α and θ-δ bands compared with HC. Occipital ΔEN α correlated significantly with MMSE, with the strongest association in the alpha band (r = 0.9000, P < 0.001).</p><p><strong>Discussion: </strong>This study applies dual-state wavelet entropy analysis to reveal impaired neural reactivity in AD during eyes-open and eyes-closed transitions. The ΔEN α metric distinguishes AD from controls and correlates with cognitive decline, reflecting reduced neural flexibility and disrupted frequency-specific network dynamics.</p><p><strong>Conclusion: </strong>This study shows that dual-state wavelet entropy analysis, especially ΔEN α, is a noninvasive tool for detecting neurodynamic abnormalities in AD. It reflects loss of state-dependent responsiveness and neural complexity, with potential for early screening and objective evaluation of treatment.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809753","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":"Subclinical Atherosclerosis Markers in Alzheimer's and Vascular Dementia: A Cross-Sectional Comparison with Healthy Controls.","authors":"Aylin Güneşli, Fazirah Hussein","doi":"10.2174/0115672050495193260728050343","DOIUrl":"https://doi.org/10.2174/0115672050495193260728050343","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular mechanisms are increasingly implicated in the pathophysiology of Alzheimer's disease and vascular dementia. This study aimed to evaluate the association between subclinical atherosclerosis markers and cognitive performance in patients with Alzheimer's disease and vascular dementia compared with healthy controls.</p><p><strong>Methods: </strong>This cross-sectional study included 79 patients with Alzheimer's disease, 69 patients with vascular dementia, and 69 age- and sex-matched controls. Vascular markers were measured, and cognitive function was assessed using the Mini-Mental State Examination. Correlation, multivariable regression, and receiver operating characteristic analyses were performed.</p><p><strong>Results: </strong>The dementia groups had greater epicardial fat thickness (Alzheimer's disease: 6.49 ± 0.93 mm; vascular dementia: 6.36 ± 1.04 mm) than controls (5.77 ± 0.87 mm, p < 0.001). Carotid intima- media thickness was higher (0.53 ± 0.08 mm and 0.55 ± 0.10 mm versus 0.48 ± 0.08 mm, p < 0.001). Carotid distensibility and strain were lower in dementia (0.21 ± 0.03 and 10.26 ± 1.58; 0.21 ± 0.03 and 9.93±1.77) than in controls (0.25 ± 0.05 and 11.3 ± 1.75, p < 0.05). Mini-Mental State Examination scores correlated negatively with epicardial fat thickness (r = -0.30) and carotid intima- media thickness (r = -0.27), and positively with distensibility (r = 0.40) and strain (r = 0.31). Epicardial fat thickness (area under the curve 0.716) and carotid intima-media thickness (0.678) showed moderate ability to distinguish dementia from controls.</p><p><strong>Discussion: </strong>These findings support a significant association between vascular structural and functional alterations and cognitive impairment.</p><p><strong>Conclusion: </strong>Subclinical atherosclerosis markers were significantly associated with cognitive impairment; however, causal relationships cannot be inferred due to the cross-sectional design. These markers may support early identification and risk stratification of dementia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809716","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":"Orexin Signaling, Glymphatic Clearance, and Preclinical Alzheimer's Disease: A Scoping Review and Hypothesis-Generating Conceptual Framework.","authors":"Ghassan Sonji, Nada Sonji, Afaf El Katerji","doi":"10.2174/0115672050487100260727051112","DOIUrl":"https://doi.org/10.2174/0115672050487100260727051112","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep fragmentation is associated with preclinical Alzheimer's disease (AD) and may precede cognitive symptoms by years. Sleep disruption is a factor amenable to objective assessment. Evidence suggests that fragmented sleep impairs the brain's glymphatic clearance system, promoting amyloid-beta and tau accumulation. This raises the possibility that dual orexin receptor antagonists (DORAs) may influence sleep-related processes in preclinical AD, though direct human evidence is lacking.</p><p><strong>Methods: </strong>This study conducted a PRISMA-ScR scoping review from 2012 to June 2025 evaluating plasma p-tau217, Aβ42/40 ratios, DTI-ALPS, sleep architecture, and APOE ε4 genotype. This study assessed evidence quality using an exploratory confidence-rating approach.</p><p><strong>Results: </strong>In some transgenic AD models, orexin antagonism reduced amyloid plaque burden. Human data remain limited. In a randomized placebo-controlled four-week trial involving 285 participants with probable AD dementia and insomnia, suvorexant significantly increased total sleep time relative to placebo. However, biomarker changes, glymphatic function, and long-term cognitive outcomes were not evaluated. Thus, current evidence for disease-modifying effects in humans is very limited and uncertain.</p><p><strong>Discussion: </strong>Whether DORAs influence glymphatic clearance in humans remains unknown. One untested mechanistic question concerns the role of noradrenergic vascular pulsations during sleep. Future trials should incorporate integrated endpoints including fluid biomarkers, neuroimaging, and sleep physiology.</p><p><strong>Conclusion: </strong>Preclinical findings remain preliminary and lack human validation. This review maps existing biomarker literature to generate mechanistic hypotheses; no integrative risk model, threshold combination, or stratification tool is proposed. Mechanistic proof-of-concept studies must precede any consideration of larger trials or translational application.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809749","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":"Safety Comparison of Acetylcholinesterase Inhibitors Using FAERS Spontaneous-Reporting Data: Drug-Specific Reporting Signals and Time-to-Onset Dynamics.","authors":"Yidan Du, Jia Li, Fei Han, Jianjun Li, Hong Lin, Fangfang Ge","doi":"10.2174/0115672050497124260720115932","DOIUrl":"https://doi.org/10.2174/0115672050497124260720115932","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Acetylcholinesterase Inhibitors (AChEIs) are widely used for symptomatic treatment of Alzheimer's disease, but their post-marketing reporting profiles may differ. This study compared FAERS disproportional reporting signals and Time-To-Onset (TTO) patterns for donepezil, galantamine, and rivastigmine.</p><p><strong>Methods: </strong>FAERS reports from Q1 2004 to Q2 2025 were analyzed. Reports listing donepezil, galantamine, or rivastigmine as the primary suspect drug were retained. Unique case-drug-Preferred Term (PT) triplets were constructed after case-level and drug-event-level de-duplication. Positive signals were defined conservatively by the intersection of ROR, PRR, BCPNN, and MGPS/EBGM criteria. TTO was evaluated using cumulative onset-distribution curves, Weibull models, and Accelerated Failure-Time (AFT) models.</p><p><strong>Results: </strong>The analysis included 9,474 donepezil reports, 3,042 galantamine reports, and 14,666 rivastigmine reports. The four-method intersection identified 286 positive PT reporting signals for donepezil, 143 for galantamine, and 259 for rivastigmine. Donepezil showed prominent cardiac reporting signals, including sinus bradycardia (ROR = 49.0) and electrocardiogram QT prolongation (ROR = 16.75). Rivastigmine showed application-site signals, including application-site erythema (ROR = 21.36) and application-site pruritus (ROR = 18.07). Galantamine showed signals including bradycardia (ROR = 15.37), fall (ROR = 3.44), and decreased appetite (ROR = 3.57). Median TTOs were 38, 44, and 64 days for donepezil, galantamine, and rivastigmine, respectively. Rivastigmine showed a later reported onset than donepezil in the AFT model (TR = 1.08; p = 0.008).</p><p><strong>Discussion: </strong>The findings suggest shared cholinergic reporting patterns and drug-specific signal profiles. Because FAERS lacks exposure denominators, these results indicate disproportional reporting rather than incidence, causality, or comparative clinical risk.</p><p><strong>Conclusion: </strong>Donepezil, galantamine, and rivastigmine showed distinct FAERS reporting profiles and early post-initiation TTO patterns. These findings are hypothesis-generating and require confirmation in independent pharmacovigilance or clinical datasets.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809720","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":"Descriptive Analysis of Genetic Variants in Individuals Without a Clinical Diagnosis of Alzheimer's Disease in a Population from Southwestern Colombia.","authors":"Liliana Doza Martinez, Helen Johana Ortiz Rojas, Jorge Hernán Izquierdo Loaiza, Daniela Arturo Terranova, Felipe García, José María Satizabal","doi":"10.2174/0115672050477248260724105245","DOIUrl":"https://doi.org/10.2174/0115672050477248260724105245","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is the most common cause of dementia worldwide and a chronic neurodegenerative disorder with well-established pathophysiological mechanisms. In Colombia, its prevalence is increasing, but in the southwestern region, information on its clinical course is scarce, limiting adequate care and public health strategies. This study aimed to describe the frequency and characteristics of genetic variants in AD candidate genes in a population in southwestern Colombia without a clinical diagnosis of the disease.</p><p><strong>Methods: </strong>A descriptive observational analysis was conducted on 320 whole exomes from patients without a clinical diagnosis of AD. Reported genomic variants in the APOE, ABCA7, APP, PSEN1, PSEN2, and CLU genes were examined for allele frequency, clinical significance, and interaction network predictions to assess their genetic impact on the population.</p><p><strong>Results: </strong>We identified 294 genetic variants, including 267 previously unreported. Among the 27 variants reported in ClinVar, most lacked a definitive clinical interpretation and were classified as Variants of Uncertain Significance (VUS) or as variants without a defined clinical significance in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). ABCA7 gene had the highest frequency of variants (n=164), and the PSEN1 gene had the lowest (n=14). While most variants lacked clinical significance, the APOE c.487C>T (p.Arg163Cys) variant was identified as likely pathogenic.</p><p><strong>Discussion: </strong>The genetics of AD are complex and contribute to a predisposition to developing the disease; hence, the importance of conducting studies in our Colombian population, which is characterized by great genetic variability. In our study, we identified 267 unreported variants associated with the genes APOE, ABCA7, APP, PSEN1, PSEN2, and CLU. The lack of updated data in our population underscores the need for further research to determine their clinical impact.</p><p><strong>Conclusion: </strong>This research contributes to characterizing AD genetic variability in the Colombian population and identifies several previously unreported variants. According to our results, we recommend studying their potential functional and clinical impact to improve early diagnosis and support the development of targeted therapies, thereby contributing to a better understanding of the disease in southwestern Colombia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809710","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 Black Hole of the Brain: A Novel Energy-Based Therapeutic Perspective for Alzheimer's Disease.","authors":"Shima Motamedi, Isaac Karimi","doi":"10.2174/0115672050438652260723053125","DOIUrl":"https://doi.org/10.2174/0115672050438652260723053125","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is considered a devastating and often underrecognized global health burden. Despite extensive ongoing research, effective treatments remain limited by an incomplete understanding of its multifarious pathogenesis, more than a century since the first report of AD in 1906. This review proposes a novel conceptual framework that draws parallels between entropy- driven systemic collapse in physical systems and neurodegeneration in AD. Specifically, it highlights how entropy may lead to systemic collapse, whether in a dead star that forms a black hole or in an AD-afflicted brain region. Though differing in biological and physical scales, AD and black holes share analogous features, including rising entropy, irreversible degeneration, and system decay, that are fundamental to understanding their underlying physics. Both AD and black holes represent systems characterized by irreversible loss of structure, energy, and information. In AD, progressive neural death leads to cognitive impairment, synapse loss, and brain atrophy, reflecting impaired energy utilization and increasing entropy within neural networks. Similarly, a black hole forms from stellar collapse, where energy becomes gravitationally confined and entropy increases as information is lost beyond the event horizon. Diagnostic exploration of both phenomena relies on interpreting waves and signals, neuroimaging in the brain, and the detection of electromagnetic or gravitational waves in space, revealing how the breakdown of structure and the dissipation of accessible energy signify a fundamental loss of order in complex systems. This conceptual framework may help inspire innovative energy-based therapeutic approaches for AD before the disease reaches an irreversible stage of pathogenesis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809745","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}