Insulin Levels are Decreased in the Cerebrospinal Fluid of Women with Prodomal Alzheimer's Disease

Previous studies have failed to reach consensus on insulin levels in cerebrospinal fluid of Alzheimer's disease (AD) patients and on its relation to pathological features. We performed a new analysis in patients at different stages of AD, and investigated the relationship of insulin levels with biochemical disease markers and with cognitive score. We included 99 patients from our Memory Clinic (Karolinska University Hospital, Sweden), including: 27 patients with mild AD, 13 that progressed from mild cognitive impairment (MCI) to AD in two years time, 26 with MCI stable after two years, and 33 with subjective cognitive impairment. Insulin was significantly decreased in the cerebrospinal fluid of both women and men with mild AD. Insulin deficits were seen in women belonging to both MCI groups, suggesting that this occurs earlier than in men. Insulin was positively associated with amyloid-β 1–42 (Aβ_1–42) levels and cognitive score. Furthermore, total-tau/(Aβ_1–42*insulin) ratio showed strikingly better sensitivity and specificity than the total-tau/Aβ_1–42 ratio for early AD diagnosis in women.