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.


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*


  • 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