Biomarker profiling beyond amyloid and tau: cerebrospinal fluid markers, hippocampal atrophy, and memory change in cognitively unimpaired older adults

Ane-Victoria Idland; Roser Sala-Llonch; Leiv Otto Watne; Anne Brækhus; Oskar Hansson; Kaj Blennow; Henrik Zetterberg; Øystein Sørensen; Kristine Beate Walhovd; Torgeir Bruun Wyller; Anders Martin Fjell

doi:10.1016/j.neurobiolaging.2020.04.002

Biomarker profiling beyond amyloid and tau: cerebrospinal fluid markers, hippocampal atrophy, and memory change in cognitively unimpaired older adults

Neurobiol Aging. 2020 Sep:93:1-15. doi: 10.1016/j.neurobiolaging.2020.04.002. Epub 2020 Apr 15.

Authors

Affiliations

¹ Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: av.idland@gmail.com.
² Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
³ Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁴ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Clinical Sciences, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Lund, Sweden.
⁶ Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
⁸ Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
⁹ Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
¹⁰ Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.

PMID: 32438258
DOI: 10.1016/j.neurobiolaging.2020.04.002

Abstract

Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain β-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aβ42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline.

Keywords: Beta amyloid 1–42; Biomarkers; Cerebrospinal fluid; Chitinase-3-like protein 1; Fatty acid binding protein 3; Hippocampal atrophy; Magnetic resonance imaging; Memory; Neurofilament light; Phosphorylated tau; Total tau.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Aging / cerebrospinal fluid*
Aging / pathology*
Aging / psychology
Amyloid beta-Peptides / cerebrospinal fluid*
Atrophy
Biomarkers / cerebrospinal fluid
Chitinase-3-Like Protein 1 / cerebrospinal fluid*
Cognitive Dysfunction / diagnosis*
Fatty Acid Binding Protein 3 / cerebrospinal fluid
Female
Hippocampus / pathology
Humans
Male
Memory*
Middle Aged
Neurofilament Proteins / cerebrospinal fluid
Peptide Fragments / cerebrospinal fluid*
Predictive Value of Tests
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Biomarkers
CHI3L1 protein, human
Chitinase-3-Like Protein 1
FABP3 protein, human
Fatty Acid Binding Protein 3
Neurofilament Proteins
Peptide Fragments
amyloid beta-protein (1-42)
neurofilament protein L
tau Proteins