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Updated: Aug 4, 2025
A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer Formation
Published on: March 27, 2017
Annual stability of the plasma Aß40/42 ratio and associated factors
Takumi Nakamura1,2, Takeshi Kawarabayashi1,2,3, Naoko Nakahata2,4
1Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
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.
