Amyloid-β positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to lower hippocampal volume

Neurobiol Aging. 2021 Aug;104:24-31. doi: 10.1016/j.neurobiolaging.2021.02.026. Epub 2021 Mar 6.


Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes. Interactions with Aβ were also explored. Individuals with SCD had higher CSF NfL and lower CSF Aβ42/40 than Controls. There was a significant interaction between SCD and CSF-Aβ42/40 levels. Stratified analyses showed a significant association between SCD and NfL only in Aβ+ individuals. Higher CSF NfL was significantly associated with lower hippocampal volume specifically in Aβ+ individuals with SCD. The presence of SCD in Aβ+ individuals may represent an early symptom in the Alzheimer's continuum related to incipient neurodegeneration.

Keywords: Amyloid-beta; Biomarkers; CSF; Hippocampal volume; Neurofilament light; Subjective cognitive decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / metabolism*
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology*
  • Female
  • Hippocampus / pathology*
  • Humans
  • Male
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid*
  • Organ Size


  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L