title: Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients.
abstract: Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C(11)]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Corlier
authors.affiliation: 201;quipe de Statistique Appliquée, ESPCI ParisTech, PSL Research University, INSERM UMRS 1158, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Rivals
authors.affiliation: Neurologie de la Mémoire et du Langage, Service de Neurologie, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Lagarde
authors.affiliation: Neurologie de la Mémoire et du Langage, Service de Neurologie, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Hamelin
authors.affiliation: Neurologie de la Mémoire et du Langage, Service de Neurologie, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Corne
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Dauphinot
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Ando
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Cossec
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Fontaine
authors.affiliation: 1] INSERM UMRS 938, Laboratoire Système Immunitaire et Maladies Conformationnelles, Hôpital Saint-Antoine, Paris, France [2] Université Pierre et Marie Curie, Université Paris 6, Centre de Recherche Saint-Antoine, Hôpital Saint-Antoine, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Dorothée
authors.affiliation: 1] Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie-Endocrinologie-Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France [2] UR AFPA-USC 340, Equipe BFLA, Université de Lorraine, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Malaplate-Armand
authors.affiliation: 1] Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie-Endocrinologie-Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France [2] UR AFPA-USC 340, Equipe BFLA, Université de Lorraine, Nancy, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Olivier
authors.affiliation: Institut de la mémoire et de la maladie d'Alzheimer, IMMA, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.affiliation: CEA (MB), DSV, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: M
authors.initials: M
authors.lastname: Bottlaender
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France [4] Laboratoire de Neuropathologie Escourolle, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Neurologie de la Mémoire et du Langage, Service de Neurologie, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Sarazin
authors.affiliation: 1] UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France [2] INSERM U 1127, Paris, France [3] ICM Research Centre, CNRS UMR 7225, Paris, France.
authors.forename: M-C
authors.initials: MC
authors.lastname: Potier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D011992:Endosomes / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins