Prospective Associations between Plasma Amyloid-Beta 42/40 and Frailty in Community-Dwelling Older Adults

J Prev Alzheimers Dis. 2021;8(1):41-47. doi: 10.14283/jpad.2020.60.


Background: Brain amyloid-beta (Aβ) plaques, a hallmark of the pathophysiology of Alzheimer's disease, have been associated with frailty. Whether the plasma Aβ markers show similar relationship with frailty is unknown.

Objectives: To investigate the prospective associations between plasma Aβ42/40 ratio and overtime frailty in community-dwelling older adults.

Methods: From the 5-year Multidomain Alzheimer Preventive Trial (MAPT), we included 477 adults ≥70 years with available data on plasma Aβ42/40 ratio (lower is worse). Fried frailty phenotype (robust, pre-frail and frail) was assessed at the same time-point of plasma Aβ measures and after until the end of follow-up. The outcomes of interest were the change in the frailty phenotype over time (examined by mixed-effect ordinal logistic regressions) and incident frailty (examined by Cox proportional hazard models).

Results: Plasma Aβ42/40 did not show significant associations with incident frailty; however, after adjusting for Apolipoprotein E (APOE) ε4 genotype, people in the lower quartile of plasma Aβ42/40 (≤0.103) had higher risk of incident frailty (HR=2.63; 95% CI, 1.00 to 6.89), compared to those in the upper quartile (>0.123). Exploratory analysis found a significant association between the lower quartile of plasma Aβ42/40 and incident frailty among APOE ε4 non-carriers (HR=3.48; 95% CI, 1.19 to 10.16), but not among carriers. No associations between plasma Aβ42/40 and evolution of frailty were observed.

Conclusion: No significant associations between plasma Aβ42/40 and frailty were found when APOE ε4 status was not accounted into the model. Nevertheless, APOE ε4 non-carriers with high Aβ burden might be more susceptible to develop frailty.

Keywords: Frailty; amyloid-beta; biomarker; neurodegeneration; older adults.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / blood*
  • Apolipoprotein E4 / genetics
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Frailty / blood*
  • Frailty / diagnosis
  • Frailty / genetics
  • Humans
  • Independent Living / statistics & numerical data*
  • Longitudinal Studies
  • Male
  • Peptide Fragments / blood*
  • Proportional Hazards Models


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)