Alzheimer's Research & Therapy最新文献

{"title":"Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.","authors":"Lidia Canals-Gispert, Alba Cañas-Martínez, Gema Huesa, Marc Suárez-Calvet Alomà, Marta Milà-Alomà, Eider Arenaza-Urquijo, Davide Cirillo, Annemarie Schumacher Dimech, Maria Florencia Iulita, Julie Novakova Martinkova, Maria Carmela Tartaglia, Frances-Catherine Quevenco, Antonella Santuccione Chadha, Gonzalo Sánchez-Benavides, Carolina Minguillón, Maria Teresa Ferretti, Karine Fauria, Anna Brugulat-Serrat","doi":"10.1186/s13195-024-01626-1","DOIUrl":"10.1186/s13195-024-01626-1","url":null,"abstract":"<p><strong>Background: </strong>Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.</p><p><strong>Methods: </strong>This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment). Sociodemographic data on education, occupational attainment, civil and caregiver status were gathered. Stepwise logistic regression models were performed in order to study the interaction between gender and sociodemographic factors in the willingness to participate in clinical trials and to undergo clinical trial-related procedures.</p><p><strong>Results: </strong>1,606 out of the 2,544 participants were women (63.1%). Women were significantly younger and had lower educational attainment compared with men. In addition, women were more likely to be caregivers, single and unemployed. Women showed a significantly lower willingness than men to participate in a clinical trial (p = 0.003) and to undergo a lumbar puncture (p < 0.001). Single women were less willing to participate in clinical trials than single men (p = 0.041). Regarding clinical trial-related procedures, women with higher years of education were significantly less willing to undergo a lumbar puncture (p = 0.031).</p><p><strong>Conclusion: </strong>We found gender differences regarding the sociodemographic factors that predict the willingness to participate in clinical trials and to undergo clinical trial-related procedures. Our results highlight the urgent need to design recruitment strategies accounting for gender-related factors, particularly those related to marital status and education.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"263"},"PeriodicalIF":7.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862769","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":"Intracerebral hemorrhage following mild ARIA-H in an APOE ε2 carrier receiving lecanemab.","authors":"Sung Ji, Michael Rosenbloom","doi":"10.1186/s13195-024-01640-3","DOIUrl":"10.1186/s13195-024-01640-3","url":null,"abstract":"<p><strong>Objective: </strong>Report a case of an apolipoprotein E (APOE)ε2 carrier receiving lecanemab who developed late onset intracerebral hemorrhage (ICH) following amyloid-related imaging abnormalities-hemorrhage (ARIA-H).</p><p><strong>Method: </strong>We detail the history and neuroimaging findings of a 73-year-old male with Alzheimer's disease (APOEε2/ε3 status) who developed ICH after mild ARIA-H and suffering a fall.</p><p><strong>Results: </strong>The patient developed mild ARIA-H after his 13th infusion that was proceeded by left temporo-occipital hemorrhage following his 14th infusion.</p><p><strong>Discussion: </strong>Although APOE ε2 is known to be protective against Alzheimer's disease, it has also been shown to increase risk for hemorrhage with cerebral amyloid angiopathy. This case serves as an opportunity to examine the complex role that APOE ε2 plays in both protection against Alzheimer's disease and contribution to increased hemorrhagic risk with lecanemab.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"265"},"PeriodicalIF":7.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862893","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":"Response to Schmidt et al.: Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis.","authors":"Emma L Anderson","doi":"10.1186/s13195-024-01631-4","DOIUrl":"10.1186/s13195-024-01631-4","url":null,"abstract":"<p><p>A recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson's dementia. Alzheimer's disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer's risk and may even potentially modestly increase risk. There is also little evidence to support an effect of CETP inhibition on all-cause or vascular dementia. Thus, CETP inhibition is unlikely to be a viable target to treat the most prevalent causes of dementia.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"264"},"PeriodicalIF":7.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862896","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":"Analytical and clinical performance of eight Simoa^® and Lumipulse^® assays for automated measurement of plasma p-tau181 and p-tau217.","authors":"Anna L Wojdała, Jeroen Vanbrabant, Sherif Bayoumy, Daniel Antwi-Berko, Nathalie Le Bastard, Wiesje M van der Flier, Andreas Jeromin, Charlotte Lambrechts, Maxime Van Loo, Manu Vandijck, Erik Stoops, Inge M W Verberk, Charlotte E Teunissen","doi":"10.1186/s13195-024-01630-5","DOIUrl":"10.1186/s13195-024-01630-5","url":null,"abstract":"<p><strong>Background: </strong>Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed a comprehensive method comparison study, followed by evaluation of the diagnostic performance of eight recent plasma p-tau immunoassays targeting different tau phosphorylation sites, different tau fragments, and that are measured by two distinct platforms.</p><p><strong>Methods: </strong>We enrolled a cohort of 40 patients with AD at the stage of dementia (AD-dem) characterized by positive CSF A + T + profile, and a control group of 40 cognitively healthy participants (Control), to conduct a comprehensive method comparison for three plasma p-tau181 and five plasma p-tau217 assays run on the Simoa^® HD-X™ or Lumipulse^® G600II/G1200 platforms. Design of the compared assays differed in regard to: (1) tau phosphorylation site targeted by the capture antibody (T181 or T217), and (2) epitope of the pan-tau detector antibody (N-terminal or mid-region). For each of the assays we determined precision and analytical sensitivity parameters and used Passing-Bablok regression and Bland-Altman plots for pairwise comparison of p-tau181 or p-tau217 assays. Subsequently, we evaluated the diagnostic accuracy of all the assays for discrimination between AD-dem and Control groups.</p><p><strong>Results: </strong>We found a strong, positive correlation between all the measurements. Fixed and/or proportional bias was observed for each of compared p-tau181 assay pairs or p-tau217 assay pairs. While both plasma p-tau181 and p-tau217 levels were significantly increased in AD-dem vs. Control groups as measured by all assays, higher median concentration AD-dem/Control fold change and AUC values were observed for p-tau217 (assays range: fold change 3.72-6.74, AUC 0.916-0.956) compared with p-tau181 (assays range 1.81-2.94, AUC 0.829-0.909), independently of the platform used. No significant differences were observed between diagnostic performance of p-tau181 assays or p-tau217 assays targeting tau N-terminus or mid-region.</p><p><strong>Conclusions: </strong>Although all plasma p-tau measurements enabled discrimination between clinical groups, p-tau217 assays showed the highest robustness, independently of the pan-tau detector antibody targeting N-terminal or mid-region, and independently of the platform used. Considering the observed method disagreement in measured absolute concentrations, we stress the need for development of certified reference material, harmonizing measurements across different platforms.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"266"},"PeriodicalIF":7.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862768","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":"Greater baseline cortical atrophy in the dorsal attention network predicts faster clinical decline in Posterior Cortical Atrophy.","authors":"Yuta Katsumi, Ryan Eckbo, Marianne Chapleau, Bonnie Wong, Scott M McGinnis, Alexandra Touroutoglou, Bradford C Dickerson, Deepti Putcha","doi":"10.1186/s13195-024-01636-z","DOIUrl":"10.1186/s13195-024-01636-z","url":null,"abstract":"<p><strong>Background: </strong>Posterior Cortical Atrophy (PCA) is a clinical syndrome characterized by progressive visuospatial and visuoperceptual impairment. As the neurodegenerative disease progresses, patients lose independent functioning due to the worsening of initial symptoms and development of symptoms in other cognitive domains. The timeline of clinical progression is variable across patients, and the field currently lacks robust methods for prognostication. Here, evaluated the utility of MRI-based cortical atrophy as a predictor of longitudinal clinical decline in a sample of PCA patients.</p><p><strong>Methods: </strong>PCA patients were recruited through the Massachusetts General Hospital Frontotemporal Disorders Unit PCA Program. All patients had cortical thickness estimates from baseline MRI scans, which were used to predict longitudinal change in clinical impairment assessed by the CDR Sum-of-Boxes (CDR-SB) score. Multivariable linear regression was used to estimate the magnitude of cortical atrophy in PCA patients relative to a group of amyloid-negative cognitively unimpaired participants. Linear mixed-effects models were used to test hypotheses about the utility of baseline cortical atrophy for predicting longitudinal clinical decline.</p><p><strong>Results: </strong>Data acquired from 34 PCA patients (mean age = 65.41 ± 7.90, 71% females) and 24 controls (mean age = 67.34 ± 4.93, 50% females) were analyzed. 62% of the PCA patients were classified as having mild cognitive impairment (CDR 0.5) at baseline, with the rest having mild dementia (CDR 1). Each patient had at least one clinical follow-up, with the mean duration of 2.78 ± 1.62 years. Relative to controls, PCA patients showed prominent baseline atrophy in the posterior cortical regions, with the largest effect size observed in the visual network of the cerebral cortex. Cortical atrophy localized to the dorsal attention network, which supports higher-order visuospatial function, selectively predicted the rate of subsequent clinical decline.</p><p><strong>Conclusions: </strong>These results demonstrate the utility of a snapshot measure of cortical atrophy of the dorsal attention network for predicting the rate of subsequent clinical decline in PCA. If replicated, this topographically-specific MRI-based biomarker could be useful as a clinical prognostication tool that facilitates personalized care planning.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"262"},"PeriodicalIF":7.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852027","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":"Frequency, sociodemographic, and neuropsychological features of patients with subjective cognitive decline diagnosed using different neuropsychological criteria.","authors":"Pedro Câmara Pestana, Sandra Cardoso, Manuela Guerreiro, João Maroco, Frank Jessen, Frederico Simões do Couto, Alexandre de Mendonça","doi":"10.1186/s13195-024-01634-1","DOIUrl":"10.1186/s13195-024-01634-1","url":null,"abstract":"<p><strong>Background: </strong>Subjective Cognitive Decline (SCD) is recognized as a risk stage for future cognitive impairment and dementia. The criteria for SCD include normal performance on neuropsychological testing; however, there is a lack of consensus regarding standard score cut-offs for neuropsychological tests to define cognitive impairment and to differentiate between SCD and Mild Cognitive Impairment (MCI). This study aimed to assess the frequency of SCD diagnosis using various neuropsychological definitions of cognitive normality and to characterize the sociodemographic and neuropsychological features of SCD patients diagnosed under these criteria.</p><p><strong>Methods: </strong>The Cognitive Complaints Cohort (CCC) participants were diagnosed following Subjective Cognitive Decline Initiative (SCD-I) criteria. Normal cognitive performance was defined by the absence of Mild Cognitive Impairment (MCI) according to the five sets of MCI neuropsychologically based criteria defined by Jak and Bondi. Descriptive statistics were used to analyze sociodemographic, clinical, and neuropsychological data. A bootstrap methodology was employed to estimate the mean and 95% confidence intervals (CI) for specific parameters of interest, namely the SMC scale (subjective memory complaints scale), Mini-Mental State Examination (MMSE), Blessed Dementia Rating Scale - first part (BDRS first part), and Geriatric Depression Scale (GDS).</p><p><strong>Results: </strong>Among the 1268 subjects included, the prevalence of SCD diagnosis exhibited substantial variation across SCD-I criteria using different neuropsychological definitions of cognitive normality (ranging from 16.4 to 81.3%). When using the most conservative criteria to define cognitive impairment (2 tests within a cognitive domain > 1.5 SD below age-adjusted means), the resulting Conservative SCD group had poorer global cognitive function (MMSE: mean 27.15, 95% CI 27.00-27.31), whereas when using the most liberal criteria to define cognitive impairment (only one test > 1 SD below age-adjusted means) the resulting Liberal SCD group had superior performance in daily-life functioning (BDRS first part: mean 0.30, 95% CI 0.23-0.38). However, subjective cognitive complaints and neuropsychiatric symptoms did not significantly differ among SCD diagnostic groups.</p><p><strong>Conclusions: </strong>The utilization of diagnostic criteria using distinct neuropsychological definitions of cognitive normality significantly impacts the frequency of SCD diagnosis and characterizes different patient populations. Consequently, it is essential to specify the criterion when diagnosing a SCD patient and to understand the risks and benefits of using different criteria to define cognitive impairment.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"261"},"PeriodicalIF":7.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783855","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: Different associations between body mass index and Alzheimer's markers depending on metabolic health.","authors":"Eun Hye Lee, Heejin Yoo, Young Ju Kim, Bo Kyoung Cheon, Seungho Ryu, Yoosoo Chang, Jihwan Yun, Hyemin Jang, Jun Pyo Kim, Hee Jin Kim, Seong-Beom Koh, Jee Hyang Jeong, Duk L Na, Sang Won Seo, Sung Hoon Kang","doi":"10.1186/s13195-024-01625-2","DOIUrl":"https://doi.org/10.1186/s13195-024-01625-2","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"260"},"PeriodicalIF":7.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765435","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":"Alzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.","authors":"Kyonghwan Choe, Muhammad Ali, Roy Lardenoije, Renzo J M Riemens, Ehsan Pishva, Horst Bickel, Siegfried Weyerer, Per Hoffmann, Michael Pentzek, Steffi Riedel-Heller, Birgitt Wiese, Martin Scherer, Michael Wagner, Diego Mastroeni, Paul D Coleman, Alfredo Ramirez, Inez H G B Ramakers, Frans R J Verhey, Bart P F Rutten, Gunter Kenis, Daniel L A van den Hove","doi":"10.1186/s13195-024-01623-4","DOIUrl":"https://doi.org/10.1186/s13195-024-01623-4","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.</p><p><strong>Methods: </strong>DNA derived from post-mortem middle temporal gyrus (MTG) tissue from AD patients (n = 45) and age-matched controls (n = 35) was analyzed, along with DNA derived from blood samples from two independent cohorts: the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) cohort (n = 96) and the Dutch BioBank Alzheimer Center Limburg (BBACL) cohort (n = 262). Molecular profiling, including assessing mRNA expression and DNA (hydroxy)methylation levels, was conducted using HumanHT-12 v4 Expression BeadChip and HM 450 K BeadChip arrays, respectively. Functional interactions between genes and identification of common phenotype-specific positive and negative elementary circuits were conducted using computational modeling, i.e. gene regulatory network (GRN) and network perturbational analysis. DNA methylation of IDO2 (cg11251498) was analyzed using pyrosequencing.</p><p><strong>Results: </strong>Twelve TRP- and twenty NAD-associated genes were found to be differentially expressed in the MTG of AD patients. Gene sets associated in the kynurenine pathway, the most common TRP pathway, and NAD pathway, showed enrichment at the mRNA expression level. Downstream analyses integrating data on gene expression, DNA (hydroxy)methylation, and AD pathology, as well as GRN and network perturbation analyses, identified IDO2, an immune regulatory gene, as a key candidate in AD. Notably, one CpG site in IDO2 (cg11251498) exhibited significant methylation differences between AD converters and non-converters in the AgeCoDe cohort.</p><p><strong>Conclusion: </strong>These findings reveal substantial transcriptional and epigenetic alterations in TRP- and NAD-pathway-associated genes in AD, highlighting IDO2 as a key candidate gene for further investigation. These genes and their encoded proteins hold potential as novel biomarkers and therapeutic targets for AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"259"},"PeriodicalIF":7.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765432","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: Glymphatic inhibition exacerbates tau propagation in an Alzheimer's disease model.","authors":"Douglas M Lopes, Jack A Wells, Da Ma, Lauren Wallis, Daniel Park, Sophie K Llewellyn, Zeshan Ahmed, Mark F Lythgoe, Ian F Harrison","doi":"10.1186/s13195-024-01624-3","DOIUrl":"10.1186/s13195-024-01624-3","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"258"},"PeriodicalIF":7.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738109","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":"Head-to-head comparison of tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.","authors":"Matteo Tonietto, Oscar Sotolongo-Grau, Núria Roé-Vellvé, Santiago Bullich, Juan Pablo Tartari, Ángela Sanabria, Ainhoa García-Sánchez, Edilio Borroni, Christopher Galli, Esther Pérez-Martínez, Joan Castell-Conesa, Isabel Roca, Lluís Tárraga, Agustín Ruiz, Andrew W Stephens, Mercè Boada, Gregory Klein, Marta Marquié","doi":"10.1186/s13195-024-01622-5","DOIUrl":"10.1186/s13195-024-01622-5","url":null,"abstract":"<p><strong>Background: </strong>Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in the early stages of the AD continuum.</p><p><strong>Methods: </strong>Data from the TAU-PET FACEHBI clinical trial (EUDRA-CT 2021-000473-83) were analyzed. All participants were non-demented and underwent tau imaging with [¹⁸F]PI-2620 and [¹⁸F]RO948 PET within 3 months, amyloid imaging with [¹⁸F]Florbetaben and brain magnetic resonance imaging. Tau PET standardized uptake values ratios (SUVR) were calculated in Braak and typical off-target regions using the inferior cerebellar cortex as a reference region.</p><p><strong>Results: </strong>The cohort consisted of 18 individuals with subjective cognitive decline (n = 13) and mild cognitive impairment (n = 5), with centiloid values ranging from 17 to 159. Both tau tracers showed similar tau pathology distribution but presented a distinct off-target signal pattern on visual read. SUVR measurements for [¹⁸F]PI-2620 and [¹⁸F]RO948 were highly correlated in all Braak regions (R² range [0.65-0.80]). Regarding off-target signal, [¹⁸F]PI-2620 had higher SUVRs in vascular structures, and [¹⁸F]RO948 had higher SUVRs in the skull/meninges.</p><p><strong>Conclusions: </strong>In a cohort of individuals at early stages of the AD continuum, tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 showed similar in-vivo uptake in all Braak regions and distinct off-target signal. These preliminary results support the development of standardized quantification scales for tau deposition that are tracer-independent.</p><p><strong>Trial registration: </strong>AEMPS EudraCT 2021-000473-83. Registered 30 December 2021.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"257"},"PeriodicalIF":7.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738116","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}