Inflammatory and Pro-resolving Mediators in Frontotemporal Dementia and Alzheimer’s Disease

Fraga, Vanêssa Gomes; Magalhães, Cíntia Lopes de Brito; Loures, Cristina de Mello Gomide; Souza, Leonardo Cruz de; Guimarães, Henrique Cerqueira; Zauli, Danielle Alves Gomes; Carvalho, Maria das Graças; Ferreira, Cláudia N.; Caramelli, Paulo; Sousa, Lirlândia P.; Gomes, Karina Braga

doi:10.1016/j.neuroscience.2019.09.008

Cited by 20 publications

(16 citation statements)

References 97 publications

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“…We found relatively few reports with extensive documentation on neuropathology, biomarker profiles, and disease progression in Latin American populations, making genotype–phenotype correlations difficult in the region. Although the use of dementia biomarkers is not widespread across Latin American countries, studies using biomarkers in FTD cohorts are available in Argentina ( 108 ), Brazil ( 109 ), and Uruguay ( 110 ). Neuroimaging studies in Latin American populations mainly describe structural findings consistent with the atrophy patterns reported in FTD studies from high-income countries.…”

Section: Resultsmentioning

confidence: 99%

Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research

et al. 2021

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Introduction: The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries.Methods: A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings.Results: The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features (n = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence (n = 4), biomarkers (n = 9), or neuropathology (n = 3) of FTD.Conclusions: Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes.

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Section: Resultsmentioning

confidence: 99%

Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research

et al. 2021

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“…During resolution, there are specialized pro-resolving mediators (SPMs) that are synthesized in endothelial cells, macrophages and neutrophils and actively participate in the transition from a proinflammatory state to a homeostatic one 97 . Only one study so far has explored alterations in SPMs in CSF and plasma so far, showing decreased levels of annexin1 in the plasma of people with bvFTD compared with AD and controls 98 .…”

Section: Resolution Pathwaymentioning

confidence: 99%

Fluid biomarkers in frontotemporal dementia: past, present and future

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Heller

et al. 2020

J Neurol Neurosurg Psychiatry

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The frontotemporal dementia (FTD) spectrum of neurodegenerative disorders includes a heterogeneous group of conditions. However, following on from a series of important molecular studies in the early 2000s, major advances have now been made in the understanding of the pathological and genetic underpinnings of the disease. In turn, alongside the development of novel methodologies for measuring proteins and other molecules in biological fluids, the last 10 years have seen a huge increase in biomarker studies within FTD. This recent past has focused on attempting to develop markers that will help differentiate FTD from other dementias (particularly Alzheimer’s disease (AD)), as well as from non-neurodegenerative conditions such as primary psychiatric disorders. While cerebrospinal fluid, and more recently blood, markers of AD have been successfully developed, specific markers identifying primary tauopathies or TDP-43 proteinopathies are still lacking. More focus at the moment has been on non-specific markers of neurodegeneration, and in particular, multiple studies of neurofilament light chain have highlighted its importance as a diagnostic, prognostic and staging marker of FTD. As clinical trials get under way in specific genetic forms of FTD, measures of progranulin and dipeptide repeat proteins in biofluids have become important potential measures of therapeutic response. However, understanding of whether drugs restore cellular function will also be important, and studies of key pathophysiological processes, including neuroinflammation, lysosomal function and synaptic health, are also now becoming more common. There is much still to learn in the fluid biomarker field in FTD, but the creation of large multinational cohorts is facilitating better powered studies and will pave the way for larger omics studies, including proteomics, metabolomics and lipidomics, as well as investigations of multimodal biomarker combinations across fluids, brain imaging and other domains. Here we provide an overview of the past, present and future of fluid biomarkers within the FTD field.

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“…For AnxA1 alone, a reduction in plasma levels was demonstrated in bvFTD patients compared to AD and controls. However, no difference was observed between AD and bvFTD in CSF ( 43 ). Another study performed in Brazil analyzed a B7-CD28/CTLA-4 pathway that is an important immunological signaling pathway involved in the modulation of T cell activation.…”

Section: Resultsmentioning

confidence: 99%

“…In a cross-sectional study of patients with a mutation in the gene CHMP2B associated frontotemporal dementia, levels of inflammatory markers such as CCL4 IL-15, CXCL10, CCL22, and TNF-α were found increased and significantly associated with cognitive decline, suggesting a peripheral inflammatory response to neurodegeneration ( 206 ). In Brazil, Fraga et al for the first time evaluated different proteins involved in the immune response in patients with FTD ( 43 ). The proteins evaluated in plasma were high sensitivity C reactive protein (hsCRP), TNF, IL-β1, IL-6, TGF-β1, LXA4, and AnxA1, and investigated changes in LXA4 e AnxA1 levels in CSF bvFTD patients.…”

Section: Resultsmentioning

confidence: 99%

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Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries

et al. 2021

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Frontotemporal dementia (FTD) includes a group of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders, affecting the fronto-insular-temporal regions of the brain. Clinically, FTD is characterized by progressive deficits in behavior, executive function, and language and its diagnosis relies mainly on the clinical expertise of the physician/consensus group and the use of neuropsychological tests and/or structural/functional neuroimaging, depending on local availability. The modest correlation between clinical findings and FTD neuropathology makes the diagnosis difficult using clinical criteria and often leads to underdiagnosis or misdiagnosis, primarily due to lack of recognition or awareness of FTD as a disease and symptom overlap with psychiatric disorders. Despite advances in understanding the underlying neuropathology of FTD, accurate and sensitive diagnosis for this disease is still lacking. One of the major challenges is to improve diagnosis in FTD patients as early as possible. In this context, biomarkers have emerged as useful methods to provide and/or complement clinical diagnosis for this complex syndrome, although more evidence is needed to incorporate most of them into clinical practice. However, most biomarker studies have been performed using North American or European populations, with little representation of the Latin American and the Caribbean (LAC) region. In the LAC region, there are additional challenges, particularly the lack of awareness and knowledge about FTD, even in specialists. Also, LAC genetic heritage and cultures are complex, and both likely influence clinical presentations and may modify baseline biomarker levels. Even more, due to diagnostic delay, the clinical presentation might be further complicated by both neurological and psychiatric comorbidity, such as vascular brain damage, substance abuse, mood disorders, among others. This systematic review provides a brief update and an overview of the current knowledge on genetic, neuroimaging, and fluid biomarkers for FTD in LAC countries. Our review highlights the need for extensive research on biomarkers in FTD in LAC to contribute to a more comprehensive understanding of the disease and its associated biomarkers. Dementia research is certainly reduced in the LAC region, highlighting an urgent need for harmonized, innovative, and cross-regional studies with a global perspective across multiple areas of dementia knowledge.

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Inflammatory and Pro-resolving Mediators in Frontotemporal Dementia and Alzheimer’s Disease

Cited by 20 publications

References 97 publications

Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research

Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research

Fluid biomarkers in frontotemporal dementia: past, present and future

Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries

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