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Biomarker-guided clustering of Alzheimer's disease clinical syndromes.
Toschi, Nicola; Lista, Simone; Baldacci, Filippo; Cavedo, Enrica; Zetterberg, Henrik; Blennow, Kaj; Kilimann, Ingo; Teipel, Stefan J; Melo Dos Santos, Antonio; Epelbaum, Stéphane; Lamari, Foudil; Genthon, Remy; Habert, Marie-Odile; Dubois, Bruno; Floris, Roberto; Garaci, Francesco; Vergallo, Andrea; Hampel, Harald.
Afiliação
  • Toschi N; Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Department of Radiology, "Athinoula A. Martinos" Center for Biomedical Imaging, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Lista S; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Baldacci F; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Cavedo E; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institut
  • Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Kilimann I; Department of Psychosomatic Medicine, University of Rostock & DZNE Rostock, Rostock, Germany.
  • Teipel SJ; Department of Psychosomatic Medicine, University of Rostock & DZNE Rostock, Rostock, Germany.
  • Melo Dos Santos A; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Epelbaum S; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Lamari F; AP-HP, UF Biochimie des Maladies Neuro-métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
  • Genthon R; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, France.
  • Habert MO; Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France; Centre pour l'Acquisition et le Traitement des Images, France; Département de Médecine Nucléaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
  • Dubois B; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Floris R; Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.
  • Garaci F; Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Casa di Cura "San Raffaele Cassino", Cassino, Italy.
  • Vergallo A; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, Paris, Franc
  • Hampel H; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Eisai Inc., Neurology Business Group, Woodcliff Lake, NJ, USA. Electronic address: harald.hampel@med.uni-muenchen.de.
Neurobiol Aging ; 83: 42-53, 2019 11.
Article em En | MEDLINE | ID: mdl-31585366
Alzheimer's disease (AD) neuropathology is extremely heterogeneous, and the evolution from preclinical to mild cognitive impairment until dementia is driven by interacting genetic/biological mechanisms not fully captured by current clinical/research criteria. We characterized the heterogeneous "construct" of AD through a cerebrospinal fluid biomarker-guided stratification approach. We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (Aß1-42, t-tau, p-tau181, NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 ± 10.4, 70.4 ± 7.7, 71.7 ± 8.4, 76.2 ± 3.5 years [mean ± SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters. We found 5 distinct clusters (sizes: N = 38, 16, 24, 14, and 21) whose composition was independent of phenotypical groups. Two clusters showed biomarker profiles linked to neurodegenerative processes not associated with classical AD-related pathophysiology. One cluster was characterized by the neuroinflammation biomarker YKL-40. Combining nonlinear data aggregation with informative biomarkers can generate novel patient strata which are representative of cellular/molecular pathophysiology and may aid in predicting disease evolution and mechanistic drug response.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteínas tau / Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteínas tau / Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article