Profiles of the composite biomarker specific for β-amyloid accumulation in the brain relevant to age and sex

Accumulation of {beta}-amyloid (A{beta}) in the brain occurs in the early phase of Alzheimers disease (AD), without symptoms of cognitive decline. Therefore, early detection of the accumulation phase is essential to prevent or delay AD. In this study, we investigated the effects of age, sex, apoprotein-E (ApoE) genotype and cognitive dysfunction on the ratio of A{beta}1-42, A{beta}1-40, and amyloid {beta} precursor protein (APP)669-711 (composite biomarker: CM) in plasma using a sensitive Time of flight mass spectrometry (TOF-MS). In healthy subjects, the average CM value of males aged 30- 59 years was significantly higher than that of females, but no difference was observed between those aged 60 and 79 years. CM values increased considerably after 50 years of age, especially in females. The effect of the ApoE4 genotype on CM was greater in females than in males. The CM value of patients with AD was higher than that of healthy subjects and that of patients with Parkinsons disease (PD). The CM value of patients with PD complicated by AD was higher than that of patients with PD. These results suggest that the CM value is influenced by age, sex, ApoE4 genotype, and central nervous system disorder. In addition, the CM value could be a reliable biomarker to distinguish not only patients with AD and healthy subjects but also AD and patients with PD. Since the measurement of CM is less invasive to the subjects, the method is helpful for the early detection of accumulation of A{beta} before the appearance of AD symptoms. Moreover, this practical method can be used for differential diagnosis among a variety of patients with dementia.