Reproductive period and preclinical cerebrospinal fluid markers for Alzheimer disease: a 25-year study

The aim of the study was to examine the association between reproductive period, as an indicator of endogenous estrogen, and levels of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD).

A population-based sample of women from Gothenburg, Sweden was followed from 1968 to 1994 (N = 75). All women had natural menopause and were free from dementia. Information on reproductive period (age at menarche to age at menopause) was obtained from interviews from 1968 to 1980. Lumbar puncture was performed from 1992 to 1994 and CSF levels of Aβ42, Aβ40, P-tau, and T-tau were measured with immunochemical methods. Linear regression models adjusted for potential confounders were used to analyze the relationship between reproductive period and CSF biomarkers for AD.

Longer reproductive period was associated with lower levels of Aβ42 (β = -19.2, P  = 0.01), higher levels of P-tau (β = 0.03, P  = 0.01), and lower ratio of Aβ42/Aβ40 (β = -0.02, P  = 0.01), while no association was observed for T-tau (β = 0.01, P  = 0.46). In separate analyses, examining the different components of reproductive period, earlier age at menarche was associated higher levels of P-tau (β = -0.07, P  = 0.031) and lower ratio of Aβ42/Aβ40 (β = 0.05, P  = 0.021), whereas no association was observed with Aβ42 (β = 31.1, P  = 0.11) and T-tau (β = -0.001, P  = 0.98). Furthermore, no association was observed between age at menopause and CSF biomarkers for AD.

Our findings suggest that longer exposure to endogenous estrogen may be associated with increased levels of AD biomarkers in the preclinical phase of AD. These findings, however, need to be confirmed in larger samples.