Citations 8
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Guen, Yann Le , Luo, Guo , Damotte, Vincent , Jansen, Iris E. , Nicolas, Aude , Rojas, Itziar de, Bellenguez, Céline , Lian, Michelle Mulan , Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier‐Boley, Benjamin , Naito, Tatsuhiko , Talyansky, Seth D., Yogeshwar, Selina , Sempere, Vicente Peris, Satake, Wataru , Álvarez, Victoria , Arosio, Beatrice , Boland, Anne , Daniele, Antonio , Darling, D.H., Dichgans, Martin , Dufouil, Carole , Düzel, Emrah , García‐Ribas, Guillermo, García‐Alberca, José María , García-González, Pablo, Giedraitis, Vilmantas , Graff, Caroline , Grünblatt, Edna , Hausner, Lucrezia , Jung, Yoo Jin , Deckert, Jürgen, Kern, Silke , Kuulasmaa, Teemu , Lee, Kun Ho , Lin, Ling , Masullo, Carlo , Mehrabian, Shima , Mendonça, Alexandre de , Boada, Merçé , Mir, Pablo , Moreno, Fermín , Nicolas, Gaël , Niida, Shumpei , Nordestgaard, Børge G. , Papenberg, Goran, Papma, Janne M., Pástor, Pau , Peters, Oliver , Popp, Julius , Molina‐Porcel, Laura , Puerta, Raquel , 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Luis Ignacio , Buiza‐Rueda, Dolores, Bürger, Katharina , Burholt, Vanessa, Cecchetti, Roberta, Chillotti, Caterina , Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher , Costantini, Emanuele Maria , Daian, Delphine , Dartigues, Jean‐François, Escott-Price, Valentina, Ewers, Michael , Fernández‐Fuertes, Marta , Ferreira, Catarina B. , Fin, Bertrand, Fließbach, Klaus , Franco-Macías, Emlio, García-González, Pablo, García‐Madrona, Sebastián, Giegling, Ina, Giorgio, Giaccone, González-Pérez, Antonio, Grande, Giulia , Green, Emma , Grimmer, Timo, Hardy, John, Hartmann, Annette M. , Harwood, Janet , Helisalmi, Seppo , Hernández, Isabel, Hoffmann, Per, Vilas, Raquel Huerto, Hulsman, Marc , Johansson, Charlotte , Kilander, Lena, Ståhlbom, Anne Kinhult, Koivisto, Anne M. , Lage, Carmen , Lerch, Ondřej , Munain, Adolfo Lopez de, Löwemark, Malin, Luckcuck, Lauren, Maier, Wolfgang, Marco, Spallazzi, Montes, Ángel Martín, Rodríguez, Carmen Martínez, Meggy, Alun, Mendoza, Silvia, Moebus, 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Proceedings of the National Academy of Sciences | August 29, 2023 | Volume: 120 | Issue: 36 | Pages: No page available
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
Missorting of plasma miRNAs in aging and Alzheimer's disease
Čarná, Mária , Novotný, Jan , Dragišić, Neda, Slavík, Hanuš , Sheardová, Kateřina , Geda, Yonas E. , Laczó, Jan , Hort, Jakub , Mao, Zixu , Dammer, Eric B. , Novotny, Jan S , Vyhnalek, Martin , Hort, Jakub , Mao, Zixu , Rissman, Robert A. , Hajduch, Marian , Dammer, Eric B , Stokin, Gorazd , Geda, Yonas E , Vyhnálek, Martin , Stokin, Gorazd B.
Journal of Neurochemistry | March 9, 2023 | Volume: 165 | Issue: 2 | Pages: 149-161
Abstract The observation that aging is regulated by microRNAs (miRNA) and at the same time represents the greatest risk factor for Alzheimer's disease (AD), prompted us to examine the circulating miRNA network in AD beyond aging. We here show that plasma miRNAs in aging are downregulated and predicted to be preferentially targeted to the extracellular vesicle (EV) content. In AD, miRNAs are further downregulated, display altered proportions of motifs relevant to their loading into EVs and secretion propensity, and are forecast to be found exclusively in EVs. The circulating miRNA network in AD, therefore, reflects pathological exacerbation of the aging process whereby physiological suppression of AD pathology by miRNAs becomes insufficient. image
Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus
Čarná, Mária , Onyango, Isaac G. , Katina, Stanislav , Holub, Dušan , Nezvedová, Markéta , Jha, Durga , Nedelská, Zuzana , Lacovich, Valentina , Houbrechts, Ruben, Garcia‐Mansfield, Krystine , David‐Dirgo, Victoria , Texlova, Kateřina, Bakkar, Nadine , Pertierra, Lucía , Vinkler, Mojmír, Marková, Hana, Laczó, Jan , Kohoutková, Marcela Hortová , Frič, Jan , Forte, Giancarlo , Bělašková, Silvie , Seyfried, Nicholas T. , Bowser, Robert , Pirrotte, Patrick , Dammer, Eric B. , Limbäck‐Stokin, Clara, Stokin, Gorazd B. , Nedelska, Zuzana , Dammer, Eric B , Novotný, Jan , Vyvere, Thijs Vande , Sharma, Ritin , Vyhnálek, Martin , Chaves, Hernán , Sheardová, Kateřina , Kaňovský, Petr , Damborský, Jiřı́ , Hort, Jakub , Sevlever, Gustavo Emilio , Rissman, Robert A. , Smith, Richard Alan , Hajduch, Marian , Spáčil, Zdeněk
Alzheimer's & Dementia | February 24, 2023 | Volume: 19 | Issue: 8 | Pages: 3537-3554
Abstract The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post‐mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. Highlights Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance
P1‐529: IMPACT OF BDNF AND APOE POLYMORPHISM ON COGNITIVE PERFORMANCE IN PATIENTS AT INCREASED RISK OF DEVELOPING ALZHEIMER'S DISEASE
Čechová, Kateřina, Chmátalová, Zuzana, Laczó, Jan , Maťoška, Václav , Kaplan, Vojtěch , Lerch, Ondřej , Andel, Ross , Vyhnálek, Martin , Nedelská, Zuzana , Hort, Jakub
Alzheimer's & Dementia | October 22, 2018 | Volume: 14 | Issue: 7S_Part_9 | Pages: No page available
Recognition of Facial Emotional Expression in Amnestic Mild Cognitive Impairment
Varjassyová, Alexandra, Hořínek, Daniel, Andel, Ross , Amlerová, Jana , Laczó, Jan , Sheardová, Kateřina , Magerová, Hana , Holmerová, Iva , Vyhnálek, Martin , Bradáč, Ondřej , Geda, Yonas E. , Hort, Jakub , Geda, Yonas E , Hort, Jakub , Vyhnalek, Martin
Journal of Alzheimer's Disease | June 4, 2018 | Volume: 33 | Issue: 1 | Pages: 273-280
P4–233: Anxiety but not depression affects self‐reported spatial navigation difficulties irrespective of the real‐space navigation performance in individuals at risk of Alzheimer's disease
Laczó, Jan , Mokrišová, Ivana, Gažová, Ivana, Sheardová, Kateřina , Vyhnálek, Martin , Nedelská, Zuzana , Telenský, Petr , Andel, Ross , Hort, Jakub
Alzheimer's & Dementia | October 9, 2013 | Volume: 9 | Issue: 4S_Part_20 | Pages: No page available
O5‐05‐06: Neuropsychological test scores are only partially associated with spatial navigation performance in amnestic mild cognitive impairment
Laczó, Jan , Gažová, Ivana, Literáková, Eva, Andel, Ross , Nedelská, Zuzana , Vlček, Kamil , Vyhnálek, Martin , Sheardová, Kateřina , Geda, Yonas E. , Hort, Jakub
Alzheimer's & Dementia | July 19, 2012 | Volume: 8 | Issue: 4S_Part_20 | Pages: No page available
P3‐097: Objective and subjective olfactory impairment in nonamnestic mild cognitive impairment
Magerová, Hana , Kadlecova, Alexandra, Laczó, Jan , Literáková, Eva, Vyhnálek, Martin , Nikolai, Tomáš , Geda, Yonas E. , Hort, Jakub
Alzheimer's & Dementia | July 19, 2012 | Volume: 8 | Issue: 4S_Part_13 | Pages: No page available