Annual stability of the plasma Aß40/42 ratio and associated factors

OBJECTIVE: The plasma Aß40/42 ratio is a biomarker of brain amyloidosis. However, the threshold difference between amyloid positivity and negativity is only 10–20% and fluctuates with circadian rhythms, aging, and APOE‐ε4 during the decades of evolution of Alzheimer's disease. METHODS: Plasma Aß40 and Aß42 levels in 1472 participants aged between 19 and 93 years in the Iwaki Health Promotion Project for 4 years were statistically analyzed. RESULTS: The means and standard deviations of annual inter‐individual coefficients of variation were 5.3 ± 3.2% for Aß40, 7.8 ± 4.6% for Aß42, and 6.4 ± 4.1% for the Aß40/42 ratio. No significant age‐dependent changes were observed in inter‐individual coefficients of variation. Age‐dependent increases in Aβ42 levels were suppressed, whereas those in the Aβ40/42 ratio were enhanced in APOE‐ε4 carriers. The change points of Aß42, Aß40, and the Aß40/42 ratio were 36.4, 38.2, and 43.5 years, respectively. In the presence of APOE‐ε4, the Aß40/42 ratio increased in middle‐aged and elderly subjects while Aβ42 levels decreased in elderly subjects. INTERPRETATION: Individual values for Aß40, Aß42, and the Aß40/42 ratio did not fluctuate annually or in an age‐dependent manner. If the plasma Aβ40/42 ratio changes by more than 14.7% (+2 standard deviations) relative to age‐ and APOE‐ε4‐adjusted normal annual fluctuations, other biomarkers also need to be examined.