Year: 2017
Type: article
Study design: Observational Study
Abstract: BACKGROUND: (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD. METHODS: APOE genotype and CSF Aβ42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17-99 from nine different clinical research centers. RESULTS: CSF concentrations of Aβ42 were lower in APOE ε4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE ε4 on CSF Aβ42 was age dependent. The age at which CSF Aβ42 concentrations started to decrease was estimated at 50 years in APOE ε4-negative individuals and 43 years in heterozygous APOE ε4 carriers. Homozygous APOE ε4 carriers showed a steady decline in CSF Aβ42 concentrations with increasing age throughout the examined age span. CONCLUSIONS: People possessing the APOE ε4 allele start to show a decrease in CSF Aβ42 concentration almost a decade before APOE ε4 noncarriers already in early middle age. Homozygous APOE ε4 carriers might deposit Aβ42 throughout the examined age span. These results suggest that there is an APOE ε4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
Source: Alzheimer s Research & Therapy
Institutions: Sahlgrenska University Hospital, University of Gothenburg, San Francisco VA Medical Center, University of California, San Francisco, Lund University, Skåne University Hospital, Karolinska Institutet, Centro San Giovanni di Dio Fatebenefratelli, University of Eastern Finland, Kuopio University Hospital, Centre National de la Recherche Scientifique, Inserm, Pitié-Salpêtrière Hospital, AXA Research Fund, Institut du Cerveau, Université Pierre-et-Marie-Curie, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,448
Funders: Torsten Söderbergs Stiftelse, Stiftelsen för Gamla Tjänarinnor, Agence Nationale de la Recherche, AXA Research Fund, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Marcus Wallenbergs Stiftelse för Internationellt Vetenskapligt Samarbete, Vetenskapsrådet, Université Pierre et Marie Curie, Commissariat Général à l'Investissement, Svenska Frimurarorden, Alzheimerfonden, Marcus och Amalia Wallenbergs minnesfond, Fondation pour la Recherche sur Alzheimer, European Research Council
OpenAlex ID: W2765110433