Sex differences of cerebrospinal fluid biomarkers in Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is more common in women than in men. Thus, to investigate the sex‐specific mechanism is important to understand the pathogenesis of AD. We examined the sex differences in levels of CSF biomarkers (tau, ptau‐181, Aβ42, HVA and 5HIAA) in AD.MethodThe subjects of this study consisted of clinically diagnosed 386 patients with AD (age 75.9±8.4 years, 237 women and 149 men). The clinical diagnosis was made based on the AD diagnostic criteria (NIA/AA, McKhann GM, et al., Alzheimers Dement 2011; 7: 263‐269). The CSF samples were obtained by lumbar puncture after informed consent was obtained. The levels of CSF tau, ptau‐181 and Aβ42 were measured by ELISA (Fujirebio, Belgium) according to the manufacturer’s protocol. The levels of CSF HVA and 5HIAA were measured by HPLC. We compared the levels of CSF biomarkers between women and men.ResultAge, the levels of CSF tau, ptau‐181 and Aβ42 showed no sex differences. The levels of CSF HVA (ng/ml) were 32.6±19.3 in women and 25.9±14.4 in men. The levels of 5HIAA were 19.1±11.7 in women and 14.8±7.7 in men. The levels of CSF HVA and 5HIAA were significantly higher in women than those in men (t‐test, HVA: p<0.001, 5HIAA: p<0.001).It has been reported that women have higher values of HVA and 5HIAA among normal subjects, due to higher monoamine oxidase (MAO) activity in women. The MAO‐A and MAO‐B genes are located on the X chromosome, and are controlled by XCI (X‐chromosome inactivation). However, the MAO genes may escape XCL MAO‐B has also been reported to be γ‐secretase associated protein and regulate neuronal amyloid β‐peptide levels. Thus, increased MAO‐B activity may be one of the reasons why AD is more common in women.ConclusionBoth CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.