Association of brain network dynamics with plasma biomarkers in subjective memory complainers

Patrizia A Chiesa; Marion Houot; Andrea Vergallo; Enrica Cavedo; Simone Lista; Marie Claude Potier; Henrik Zetterberg; Kaj Blennow; Eugeen Vanmechelen; Ann De Vos; Bruno Dubois; Harald Hampel; INSIGHT-preAD study group; Alzheimer Precision Medicine Initiative (APMI)

doi:10.1016/j.neurobiolaging.2019.12.017

Association of brain network dynamics with plasma biomarkers in subjective memory complainers

Neurobiol Aging. 2020 Apr:88:83-90. doi: 10.1016/j.neurobiolaging.2019.12.017. Epub 2019 Dec 23.

Affiliations

¹ Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. Electronic address: [email protected].
² Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France.
³ Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France.
⁴ Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Qynapse, Paris, France.
⁵ Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France.
⁶ 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 Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
⁷ 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.
⁸ UK Dementia Research Institute at UCL, London, UK; ADx NeuroSciences NV, Ghent, Belgium.
⁹ ADx NeuroSciences NV, Ghent, Belgium.
¹⁰ Eisai Inc, Neurology Business Group, Woodcliff Lake, NJ, USA.

PMID: 32087948
DOI: 10.1016/j.neurobiolaging.2019.12.017

Abstract

Using a single integrated analysis, we examined the relationship between brain networks and molecular pathways in a cohort of elderly individuals at risk for Alzheimer's disease. In 205 subjective memory complainers (124 females, mean age: 75.7 ± 3.4), individual functional connectome was computed for a total of 3081 functional connections (set A) and 6 core plasma biomarkers of Alzheimer's disease (set B) were assessed. Partial least squares correlation analysis identified one dimension of population covariation between the 2 sets (p < 0.006), which we named bioneural mode. Five core plasma biomarkers and 190 functional connections presented bootstrap ratios greater than the critical value |1.96|. T-tau protein showed a trend toward significance (bootstrap resampling = 1.64). The salience, the language, the visuospatial, and the default mode networks were the strongest significant networks. We detected a strong association between network dynamics and core pathophysiological blood biomarkers. Innovative composite biomarkers, such as the bioneural mode, are promising to provide outcomes and better inform drug development and clinical practice for neurodegenerative diseases.

Keywords: APOE; Brain functional dynamics; Integrative multimodal analysis; Plasma biomarkers; Subjective memory complaints.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease
Amyloid Precursor Protein Secretases / blood*
Amyloid beta-Peptides / blood*
Aspartic Acid Endopeptidases / blood*
Biomarkers / blood
Brain / physiopathology*
Chitinase-3-Like Protein 1 / blood*
Cohort Studies
Female
Humans
Male
Memory Disorders / diagnosis*
Memory Disorders / physiopathology*
Neural Pathways / physiopathology*
Risk
tau Proteins / blood*

Substances

Amyloid beta-Peptides
Biomarkers
CHI3L1 protein, human
Chitinase-3-Like Protein 1
tau Proteins
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
BACE1 protein, human

Grants and funding

MRC_/Medical Research Council/United Kingdom