Alzheimer's Research & Therapy最新文献

{"title":"Correction: Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.","authors":"Leslie Grasset, Cécile Proust-Lima, Jean-François Mangin, Marie-Odile Habert, Bruno Dubois, Claire Paquet, Olivier Hanon, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Renaud David, Therese Jonveaux, Catherine Belin, Adrien Julian, Isabelle Rouch-Leroyer, Jérémie Pariente, Maxime Locatelli, Marie Chupin, Geneviève Chêne, Carole Dufouil","doi":"10.1186/s13195-026-02222-1","DOIUrl":"10.1186/s13195-026-02222-1","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13741541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-interval variability and test-retest reliability of Alzheimer's disease plasma biomarkers in a clinically heterogenous cohort.","authors":"Millie Beament, Katharine Wiltshire, Christopher R S Belder, Emily Abel, Melanie Hart, Amanda J Heslegrave, Michael P Lunn, Miguel Rosa-Grilo, Owen Swann, Jonathan M Schott, Henrik Zetterberg, Nick C Fox, Ashvini Keshavan","doi":"10.1186/s13195-026-02180-8","DOIUrl":"10.1186/s13195-026-02180-8","url":null,"abstract":"<p><strong>Background: </strong>Assessment of short-term within-subject variability and test-retest reliability of Alzheimer's disease (AD)-related plasma biomarkers is important for real-world clinical implementation and interpretation in research studies. In this study we aimed to assess short-term variability and reliability of core AD plasma biomarkers, proposed ratios, and evaluate a broader proteomic panel.</p><p><strong>Methods: </strong>Two serial plasma samples were collected from each of the 92 participants enrolled in observational research studies over intervals ranging from 30 minutes to three months. Test-retest reliability and within-subject variability were assessed for 131 biomarkers measured on three immunoassays (Lumipulse G plasma p-tau217; Fujirebio, NULISAseq CNS Disease Panel and NULISAqpcr AD 5-Plex; Alamar Biosciences). We subsequently evaluated the stability of a dual cut-point approach for AD probability diagnostic categorisation and examined whether within-subject variability was associated with inter-sample interval (time between serial blood sampling).</p><p><strong>Results: </strong>All core AD plasma biomarkers assessed in this study (Aβ42, BD-p-tau181, BD-p-tau217, BD-p-tau231, p-tau181, p-tau217, p-tau231, GFAP and NfL) demonstrated strong correlations (r ≥ 0.79) and high reliability (ICC ≥ 0.84). Within-subject variability was moderate to low for core AD plasma biomarkers. Using a validated dual cut-point approach for plasma p-tau217, most individuals (92%) remained within the same diagnostic category (high/indeterminate/low) across both timepoints, and no individual moved across two boundaries (i.e. from high to low AD probability categorisation or vice versa). For the majority of analytes, within-subject variability was not associated with inter-sample interval after adjustment for age and sex, however, the core AD plasma biomarker, NfL did have a significant association.</p><p><strong>Conclusions: </strong>While core AD plasma biomarkers had limited variability and high reliability over short-intervals, other central nervous system (CNS)-relevant biomarkers showed greater variability, which may be relevant for interpretation in association studies and clinical applications.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13711881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective observational study measuring the stability of plasma pTau181 using the Elecsys Phospho-Tau (181P) plasma immunoassay for early detection of Alzheimer's disease.","authors":"Carolin Kurz, Sophia Leonhardt, Anna Hufnagel, Sabine Wizemann, Heike Deutelmoser, Patrick Menzel, Robert Perneczky","doi":"10.1186/s13195-026-02238-7","DOIUrl":"10.1186/s13195-026-02238-7","url":null,"abstract":"<p><strong>Background: </strong>Plasma tau phosphorylated at threonine 181 (pTau181) is a key blood-based biomarker that correlates with the burden of amyloid-beta (Aβ) pathology in Alzheimer's disease (AD). The Elecsys^® Phospho-Tau (181P) Plasma (pT181p) immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) is intended for use as an aid in the early detection of Aβ pathology in adults ≥ 55 years presenting with complaints of cognitive decline and is Conformité Européenne-marked and approved for clinical use by the US FDA. Here, we evaluated the stability of plasma pTau181 measured using the pT181p immunoassay under different pre-analytical and storage conditions in samples from an intended-use population.</p><p><strong>Methods: </strong>Whole blood samples from individuals presenting at LMU Hospital with symptom severity ranging from subjective cognitive decline to moderate AD dementia were collected in three different tubes for plasma preparation (Li-Heparin, K2-EDTA, and K3-EDTA). These were transported under cooled (never frozen) conditions to the measurement site and processed within 6 h of collection. Plasma samples were stored at different temperatures for varying durations, and impact on plasma pTau181 recoveries was assessed.</p><p><strong>Results: </strong>Out-of-specification results not meeting pre-defined acceptance criteria observed in an initial cohort (n = 14), were found to be the result of buffy coat/erythrocyte contamination. Pre-analytical procedures were modified to prevent contamination during post-centrifugation plasma transfer. In samples from a separate cohort (n = 10), no instabilities were observed and acceptance criteria were met. After considering safety margins, analyte stability for all sample types was determined to be 2 days at 25 °C, 7 days at 4 °C, 12 weeks at -20 °C, and 16 weeks at -80°C; stability was also observed after one freeze/thaw cycle.</p><p><strong>Conclusions: </strong>pT181p immunoassay measurements were stable and robust with respect to different sample handling procedures and storage conditions. These findings support implementation of the assay into routine, non-specialist healthcare settings to facilitate practical blood-based testing to rule out AD-related Aβ pathology.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality of people with diagnosed dementia in Germany between 2016 and 2021.","authors":"Kira Baginski, Sandra Landwehr, Manas K Akmatov, Claudia Kohring, Jens Bohlken, Stefan Teipel, Bernhard Michalowsky, Doreen Müller, Claudia Hornberg, Annika Hoyer, Jakob Holstiege","doi":"10.1186/s13195-026-02229-8","DOIUrl":"10.1186/s13195-026-02229-8","url":null,"abstract":"<p><strong>Background: </strong>Germany's aging population, driven by rising life expectancy and declining birth rates, has resulted in an increasing number of elderly individuals and various health-related challenges, with dementia being one of the most prevalent chronic diseases. Dementia is an umbrella term encompassing various medical conditions that cause progressive cognitive decline. It is linked to a substantially higher risk of death. However, data on the mortality of dementia in Germany are limited. Therefore, this study aims to estimate the all-cause mortality and mortality rate ratio (MRR) of individuals diagnosed with dementia between 2016 and 2021.</p><p><strong>Methods: </strong>The age- and sex-specific mortality of people with dementia aged 65 and older, as well as the MRR between the years 2016 and 2021, were estimated using a partial differential equation. The estimation relied on the incidence and prevalence of dementia diagnoses among individuals covered by statutory health insurance and on mortality in the general German population, sourced from the German Federal Statistical Office.</p><p><strong>Results: </strong>The standardized overall mortality of individuals diagnosed with dementia increased slightly from 18,845 to 20,238 per 100,000, reflecting a rise of 7.4% between 2016 and 2021, with males typically showing higher rates. Overall, mortality increases exponentially with age. However, the age-related mortality rates remained relatively stable from 2016 to 2021, with only a slight upward trend. Individuals with dementia had a higher risk of death compared to individuals without dementia. Females diagnosed with dementia had up to 11 times higher risk of death compared to those not diagnosed with dementia at the same age, while for males it was up to 9 times higher. This difference was most pronounced in the 65- to 70-year age group, but diminished with increasing age.</p><p><strong>Conclusions: </strong>A dementia diagnosis is associated with increased mortality across all age groups, particularly among younger individuals, although the relative risk declines with age as dementia becomes one of several comorbidities. Targeted interventions to prevent dementia, delay onset, and prolong milder stages remain essential to reduce mortality of people with dementia.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial dynamics associate with the spatial pattern of tau deposition in early Alzheimer's disease.","authors":"Marco Öchsner, Matthias Brendel, Nicolai Franzmeier, Lena Trappmann, Mirlind Zaganjori, Ersin Ersoezlue, Carolin Kurz, Jan Haeckert, Julia Utecht, Philine Marie Schirge, Boris Papazov, Oliver Pogarell, Daniel Janowitz, Katharina Buerger, Michael Ewers, Carla Palleis, Endy Weidinger, Gloria Biechele, Sebastian Schuster, Anika Finze, Florian Eckenweber, Rainer Rupprecht, Axel Rominger, Oliver Goldhardt, Timo Grimmer, Daniel Keeser, Sophia Stoecklein, Olaf Dietrich, Peter Bartenstein, Johannes Levin, Günter Höglinger, Robert Perneczky, Boris-Stephan Rauchmann","doi":"10.1186/s13195-026-02230-1","DOIUrl":"10.1186/s13195-026-02230-1","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is implicated in Alzheimer's disease (AD) pathogenesis, yet how changes in TSPO PET signal are associated with tau deposition, and how brain network architecture shapes this relationship remain poorly understood.</p><p><strong>Methods: </strong>We conducted a prospective, multimodal neuroimaging study in 56 participants: 35 amyloid-positive individuals across the AD spectrum (ADS) and 21 amyloid-negative healthy controls (HC). Amyloid status was classified primarily by CSF Aβ42/Aβ40 and, when eligible CSF was unavailable, by baseline amyloid PET. Participants underwent TSPO PET using [18 F]GE-180 and resting-state fMRI at baseline. A longitudinal subgroup additionally underwent follow-up tau PET using [18 F]PI-2620 (n = 24) and repeat TSPO PET (n = 18) approximately 18 months later.</p><p><strong>Results: </strong>Baseline TSPO did not differ significantly between groups. Baseline TSPO was associated with regional tau in both groups; the reciprocal association between tau and TSPO change was numerically weaker in AD, but this group difference was not statistically significant. Connectivity to baseline-TSPO epicenters was associated with higher tau in both groups, whereas connectivity to TSPO-change epicenters was associated with lower tau in AD but not controls (group-by-connectivity interaction p < 0.001, participant-level slope difference p = 0.012), a dissociation replicated in independent participants.</p><p><strong>Conclusion: </strong>These findings suggest that connectivity to established versus emerging TSPO epicenters carries distinct spatial information about tau in the AD spectrum, a pattern shaped by functional brain connectivity and absent in healthy controls. (ClinicalTrials.gov: NCT06224920).</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing and duration of diabetes and incident dementia in older adults: a prospective cohort study.","authors":"Lingyan Zhao, Hanbo Yu, Ruihao Song, Lin Wang, Youlie Yang, Xiaomei Wang, Jing Fan, Guiping Li","doi":"10.1186/s13195-026-02189-z","DOIUrl":"10.1186/s13195-026-02189-z","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is associated with dementia, but how this association varies with attained age and cumulative exposure remains unclear. We integrated time-updated exposure histories with repeated age-specific landmark cohorts, enabling complementary evaluation of overall and age-conditional dementia risk.</p><p><strong>Methods: </strong>We analysed 18,028 dementia-free participants aged 50 years or older from the Health and Retirement Study. Incident dementia was classified using the Langa-Weir algorithm. Time-updated Cox models evaluated risk according to current diabetes status. Age-anchored landmark models used delayed entry at six prespecified ages from 50 to 75 years. Formal age interactions and competing mortality were also assessed.</p><p><strong>Results: </strong>Diabetes was associated with higher dementia risk in the time-updated analysis (HR, 1.29; 95% CI, 1.19-1.41). The association attenuated with older attained age but remained evident across the landmark cohorts. An estimated interval exceeding 10 years since first diabetes ascertainment identified groups at higher risk. The findings remained consistent after accounting for competing death.</p><p><strong>Conclusions: </strong>Diabetes was associated with dementia throughout later life, with stronger associations at younger attained ages and among participants with a longer estimated interval since first ascertainment. These observational findings support considering the timing of diabetes ascertainment in cognitive risk assessment.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Semantic fluency predicts survival of memory clinic patients.","authors":"Lars Frings, Joachim Brumberg, Philipp T Meyer","doi":"10.1186/s13195-026-02199-x","DOIUrl":"10.1186/s13195-026-02199-x","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer's disease.","authors":"Noor Abdulhameed, Alice Babin, Kim Hansen, Riley Weaver, William A Banks, Konrad Talbot, Elizabeth M Rhea","doi":"10.1186/s13195-026-02200-7","DOIUrl":"https://doi.org/10.1186/s13195-026-02200-7","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The incremental predictive value of biological aging indicators for cognitive impairment in older adults: a longitudinal analysis on the Mr. OS & Ms. OS cohort.","authors":"Yafei Wu, Ting Zhang, Tung Wai Auyeung, Jenny Lee, Jason Leung, Timothy Kwok","doi":"10.1186/s13195-026-02198-y","DOIUrl":"10.1186/s13195-026-02198-y","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired peptide amidation and risk of incident dementia in the Malmoe preventive project cohort.","authors":"Paul Kaufmann, Yulia Ilina, Alice Giontella, Michaela Press, Katarina Nägga, Oskar Hansson, Harald Hampel, Andreas Bergmann, Olle Melander","doi":"10.1186/s13195-026-02173-7","DOIUrl":"10.1186/s13195-026-02173-7","url":null,"abstract":"<p><strong>Background: </strong>Peptidylglycine α-amidating monooxygenase (PAM) is the key enzyme responsible for the C-terminal amidation of multiple vasoactive and neuroactive peptide hormones. Among these, amidated bioactive adrenomedullin (bio-ADM) is a critical regulator of endothelial- and blood-brain barrier (BBB) integrity and vascular homeostasis. Impaired peptide amidation may contribute to endothelial dysfunction and neurovascular dysregulation, mechanisms implicated in the pathogenesis of Alzheimer's disease (AD).</p><p><strong>Methods: </strong>In 4543 dementia-free participants from the Malmö preventive project (MPP), plasma levels of mid-regional pro-adrenomedullin (MR-proADM), bio-ADM, and PAM activity (PAM-AMA) were measured at baseline, and incident dementia was ascertained through national registry data during follow-up. Associations were evaluated using Cox proportional hazards models with multivariable adjustment for common risk factors, false discovery rate correction, BMI-stratified analyses, and sensitivity analyses.</p><p><strong>Results: </strong>During a mean follow-up of 4.75 ± 1.3 years, 205 participants developed incident AD and 93 developed vascular dementia (VD). Lower PAM-AMA was associated with increased risk of incident AD (adjusted hazard ratio per 1 standard deviation decrease (aHR): 2.30; 95% confidence interval (CI): 1.31-4.02; q = 0.01). Lower bio-ADM levels were also associated with increased Alzheimer's risk (aHR: 1.62; 95% CI: 1.13-2.33; q = 0.01). A reduced bio-ADM/MR-proADM ratio and its interaction with PAM-AMA further strengthened AD risk estimates. Associations were independent of APOE ε4 carrier status, more pronounced among individuals with BMI < 30 and remained directionally consistent in sensitivity analyses. No consistent associations were observed for VD after multivariable adjustment.</p><p><strong>Conclusions: </strong>Reduced PAM-AMA and lower bio-ADM levels were associated with increased risk of incident AD, but not VD. A reduced ADM-ratio further indicates precursor peptide accumulation. These findings suggest that impaired peptide hormone amidation may represent an early systemic marker of neurovascular vulnerability and support further investigation of C-terminal peptide amidation pathways in translational AD research, including studies with a longer follow-up period and biomarker-confirmed dementia diagnoses.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}