Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures

Hum Brain Mapp. 2020 Jun 1;41(8):2004-2013. doi: 10.1002/hbm.24925. Epub 2020 Jan 16.

Abstract

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early-onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid-long form of the amyloid-beta protein [Aβ42], total-tau protein [T-tau], neurofilament light chain [NfL], neurogranin [Ng], and 14-3-3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the "AD signature" and "FTLD signature." We tested multiple regression models to find which CSF-biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14-3-3; whereas NfL and 14-3-3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.

Keywords: Alzheimer's disease; Frontotemporal Dementia; biological markers; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / cerebrospinal fluid*
  • Age of Onset
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology*
  • Diffusion Tensor Imaging
  • Female
  • Frontotemporal Dementia* / cerebrospinal fluid
  • Frontotemporal Dementia* / diagnostic imaging
  • Frontotemporal Dementia* / pathology
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neurogranin / cerebrospinal fluid*
  • Neuroimaging
  • Peptide Fragments / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*

Substances

  • 14-3-3 Proteins
  • Amyloid beta-Peptides
  • Biomarkers
  • MAPT protein, human
  • Neurofilament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • neurofilament protein L
  • tau Proteins
  • Neurogranin