Association of plasma Aβ40/Aβ42 ratio and brain Aβ accumulation: testing a whole-brain PLS-VIP approach in individuals at risk of Alzheimer's disease

Autor: Lemercier, Pablo, Vergallo, Andrea, Hampel, Harald, group, INSIGHT-preAD study, Initiative, the Alzheimer Precision Medicine, Lista, Simone, Zetterberg, Henrik, Blennow, Kaj, Potier, Marie-Claude, Habert, Marie-Odile, Lejeune, François-Xavier, Dubois, Bruno, Teipel, Stefan
Přispěvatelé: Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Gothenburg (GU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], University of Rostock, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, HAL Sorbonne Université 5, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Aging
Subjective memory
Disease
Preclinical Alzheimer's disease
0302 clinical medicine
blood [Amyloid beta-Peptides]
Cognitive impairment
Default mode network
0303 health sciences
blood [Biomarkers]
Subjective memory complaints
General Neuroscience
diagnosis [Alzheimer Disease]
Brain
3. Good health
blood [Peptide Fragments]
whole-brain
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
metabolism [Alzheimer Disease]
metabolism [Biomarkers]
Risk
metabolism [Amyloid beta-Peptides]
Partial least square
03 medical and health sciences
blood [Alzheimer Disease]
Salience (neuroscience)
Alzheimer Disease
Partial least square whole-brain
medicine
Dementia
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
ddc:610
Plasma amyloid β
Association (psychology)
diagnostic imaging [Brain]
030304 developmental biology
Aged
Amyloid beta-Peptides
business.industry
medicine.disease
Peptide Fragments
Increased risk
metabolism [Brain]
Positron-Emission Tomography
Neurology (clinical)
Geriatrics and Gerontology
business
Neuroscience
030217 neurology & neurosurgery
Biomarkers
Developmental Biology
Zdroj: Neurobiology of Aging
Neurobiology of Aging, Elsevier, 2021, 107, pp.57-69. ⟨10.1016/j.neurobiolaging.2021.07.005⟩
Neurobiology of aging 107, 57-69 (2021). doi:10.1016/j.neurobiolaging.2021.07.005
Neurobiology of Aging, 2021, 107, pp.57-69. ⟨10.1016/j.neurobiolaging.2021.07.005⟩
ISSN: 0197-4580
Popis: International audience; Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares in unraveling the association between plasma Aβ42/Aβ40 ratio and an extensive set of brain regions characterized through molecular imaging of Aβ accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma Aβ42/40 ratio was associated with Aβ-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted - including the central executive and salience networks - which likely have a selective vulnerability to incipient Aβ accumulation.The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions.
Databáze: OpenAIRE
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