Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study

Brosseron, Frederic; Kolbe, Carl-Christian; Santarelli, Francesco; Carvalho, Stéphanie; Antonell, Anna; Castro-Gomez, Sergio; Tacik, Paweł; Namasivayam, A; Mangone, Graziella; Schneider, Reinhard; Latz, Eicke; Wüllner, Ullrich; Svenningsson, Per; Castilla, Joaquı́n; Molinuevo, José Luís; Corvol, Jean‐Christophe; Heneka, Michael T.; Scordis, Philip; Hofmann‐Apitius, Martin; Lei, Johan van der; Forgó, Nikolaus; Letoha, Tamás; Georges, Jean; Graf, Ana; Canard, Luc; Lawless, Nathan; Jirsa, Viktor K.; Marovac, Jacqueline; Springstubbe, Stephan; Magnin, Éloi; Rascol, Olivier; Meissner, Wassilios; Dubois, Bruno; Epelbaum, Stéphane; Lladó, Albert; Markaki, Ioanna; Rami, Lorena; alasam, Mircea; Tsitsi, Panagiota; Cacciaglia, Raffaele; Grau, Oriol; Froehlich, Holger; Bujac, Sarah R.; Labrador, Boris; Bekadar, Samir; Bergström, Sofia; rosseron, Frederic; Nilsson, Peter; Schmitt, Imke; Page, Matthew J.; Operto, Grégory; Bosch, Beatríz; Gaudebout, Cécile; Carranza, Noemí; Gove, Dianne; Díaz, Ana Golpe; Stauch, Marc

doi:10.1016/j.jalz.2019.07.018

Cited by 35 publications

(52 citation statements)

References 33 publications

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“…As discussed above, along with other cytokines and immunoinflammatory mediators MIF reproducibly associated with tau and aging, thus suggesting that it could represent a useful diagnostic marker and therapeutic target [19].…”

Section: Discussionmentioning

confidence: 90%

“…Recent studies have also shown that immune pro-inflammatory cytokines, such as macrophage migration inhibitory factor (MIF) and YKL-40, TNF receptors and sTREM2, are associated with tau pathology and brain aging, thus suggesting that these molecules may be useful diagnostic markers and therapeutic targets [19].…”

Section: Proinflammatory Cytokines As Biomarkers During Ad Developmenmentioning

confidence: 99%

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The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

et al. 2020

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Recent preclinical and clinical observations have offered relevant insights on the etiopathogenesis of late onset Alzheimer′s disease (AD) and upregulated immunoinflammatory events have been described as underlying mechanisms involved in the development of AD. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by several cells of the innate and adaptive immune system, as well as non-immune cells. In the present review, we highlight experimental, genetic, and clinical studies on MIF in rodent models of AD and AD patients, and we discuss emerging therapeutic opportunities for tailored modulation of the activity of MIF, that may potentially be applied to AD patients. Dismantling the exact role of MIF and its receptors in AD may offer novel diagnostic and therapeutic opportunities in AD.

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Section: Discussionmentioning

confidence: 90%

Section: Proinflammatory Cytokines As Biomarkers During Ad Developmenmentioning

confidence: 99%

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

et al. 2020

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“…Integrated AETIONOMY AD. Validation data comprised 237 clinically diagnosed sporadic AD cases with available genotype from ROSMAP 72 (n = 194) and 21 additional cases with available genotype from IDIBAPS taken from the AETIONOMY biomarker verification study 73 . We call the union of these 258 AD patients integrated AETIONOMY AD in the following.…”

Section: Methodsmentioning

confidence: 99%

Clustering of Alzheimer’s and Parkinson’s disease based on genetic burden of shared molecular mechanisms

Emon

Heinson

et al. 2020

Sci Rep

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One of the visions of precision medicine has been to re-define disease taxonomies based on molecular characteristics rather than on phenotypic evidence. However, achieving this goal is highly challenging, specifically in neurology. Our contribution is a machine-learning based joint molecular subtyping of Alzheimer’s (AD) and Parkinson’s Disease (PD), based on the genetic burden of 15 molecular mechanisms comprising 27 proteins (e.g. APOE) that have been described in both diseases. We demonstrate that our joint AD/PD clustering using a combination of sparse autoencoders and sparse non-negative matrix factorization is reproducible and can be associated with significant differences of AD and PD patient subgroups on a clinical, pathophysiological and molecular level. Hence, clusters are disease-associated. To our knowledge this work is the first demonstration of a mechanism based stratification in the field of neurodegenerative diseases. Overall, we thus see this work as an important step towards a molecular mechanism-based taxonomy of neurological disorders, which could help in developing better targeted therapies in the future by going beyond classical phenotype based disease definitions.

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“…Additionally, soluble TREM2 (sTREM2) is one the of most reliable immune biomarkers in AD [ 215 ]. Most sTREM2 is produced by ADAM10 proteolysis, and this phenomenon has been linked to an increase in TREM2 signaling, thus suggesting that this receptor exerts a protective role [ 216 , 217 ].…”

Section: Genetic Risk Factors and Their Impact On Microglial Functmentioning

confidence: 99%

Microglia in Alzheimer’s Disease in the Context of Tau Pathology

2020

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Microglia are the cells that comprise the innate immune system in the brain. First described more than a century ago, these cells were initially assigned a secondary role in the central nervous system (CNS) with respect to the protagonists, neurons. However, the latest advances have revealed the complexity and importance of microglia in neurodegenerative conditions such as Alzheimer’s disease (AD), the most common form of dementia associated with aging. This pathology is characterized by the accumulation of amyloid-β peptide (Aβ), which forms senile plaques in the neocortex, as well as by the aggregation of hyperphosphorylated tau protein, a process that leads to the development of neurofibrillary tangles (NFTs). Over the past few years, efforts have been focused on studying the interaction between Aβ and microglia, together with the ability of the latter to decrease the levels of this peptide. Given that most clinical trials following this strategy have failed, current endeavors focus on deciphering the molecular mechanisms that trigger the tau-induced inflammatory response of microglia. In this review, we summarize the most recent studies on the physiological and pathological functions of tau protein and microglia. In addition, we analyze the impact of microglial AD-risk genes (APOE, TREM2, and CD33) in tau pathology, and we discuss the role of extracellular soluble tau in neuroinflammation.

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Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study

Cited by 35 publications

References 33 publications

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

Clustering of Alzheimer’s and Parkinson’s disease based on genetic burden of shared molecular mechanisms

Microglia in Alzheimer’s Disease in the Context of Tau Pathology

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