CSF level of β-amyloid peptide predicts mortality in Alzheimer's disease

Autor: Julien Dumurgier, Emmanuel Cognat, Aline Dugravot, Adla Boumenir, Matthieu Lilamand, Elodie Bouaziz-Amar, Claire Hourregue, Severine Sabia, Archana Singh-Manoux, Jean-Louis Laplanche, Jacques Hugon, Claire Paquet
Přispěvatelé: Centre de Neurologie Cognitive [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of biochemistry [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Department of Epidemiology and Public Health, University College of London [London] (UCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Bodescot, Myriam
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Apolipoprotein E
Oncology
medicine.medical_specialty
β-amyloid peptide
Neurology
Cognitive Neuroscience
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Apolipoprotein E4
Population
Kaplan-Meier Estimate
Disease
lcsh:RC346-429
lcsh:RC321-571
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Internal medicine
medicine
Humans
Mortality
education
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
CSF biomarkers
lcsh:Neurology. Diseases of the nervous system
Aged
Cause of death
education.field_of_study
Amyloid beta-Peptides
[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
business.industry
Proportional hazards model
Research
[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
Hazard ratio
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Alzheimer's disease
Peptide Fragments
3. Good health
030104 developmental biology
Biomarker (medicine)
Female
Neurology (clinical)
business
Alzheimer’s disease
Biomarkers
030217 neurology & neurosurgery
Zdroj: Alzheimer's Research and Therapy
Alzheimer's Research and Therapy, BioMed Central, 2019, 11 (1), pp.29. ⟨10.1186/s13195-019-0481-4⟩
Alzheimer’s Research & Therapy, Vol 11, Iss 1, Pp 1-9 (2019)
Alzheimer's Research & Therapy
ISSN: 1758-9193
Popis: International audience; OBJECTIVE:Alzheimer's disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10 years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD patients with high probability of AD physiopathology process assessed by positivity of three CSF biomarkers.METHODS:Three hundred twenty-one AD patients with abnormal values for CSF beta-amyloid peptide (Aβ42), tau, and phosphorylated tau levels were recruited from a memory clinic-based registry between 2008 and 2017 (Lariboisiere hospital, Paris, France) and followed during a median period of 3.9 years. We used multivariable Cox models to estimate the hazard ratio (HR) of death and institutionalization for baseline clinical data, genotype of the apolipoprotein E (APOE), and levels of CSF biomarkers.RESULTS:A total of 71 (22%) patients were institutionalized and 57 (18%) died during the follow-up. Greater age, male sex, lower MMSE score, and lower CSF Aβ42 level were associated with an increased risk of mortality. One standard deviation lower CSF Aβ42 (135 pg/mL) was associated with a 89% increased risk of death (95% CI = 1.25-2.86; p = 0.002). This association was not modified by age, sex, education, APOE ε4, and disease severity. There was no evidence of an association of tau CSF biomarkers with mortality. None of the CSF biomarkers were associated with institutionalization.CONCLUSIONS:Lower CSF Aβ42 is a strong prognostic marker of mortality in AD patients, independently of age or severity of the disease. Whether drugs targeting beta-amyloid peptide could have an effect on mortality of AD patients should be investigated in future clinical trials.
Databáze: OpenAIRE
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