Peripheral Markers of Neurovascular Unit Integrity and Amyloid-ß in the Brains of Menopausal Women.

ABSTRACT

BACKGROUND: The identification of blood-borne biomarkers for the diagnosis and prognosis of Alzheimer's disease and related dementias is more feasible at the population level than obtaining cerebrospinal fluid or neuroimaging markers. OBJECTIVE: This study determined the association of blood microvesicles, derived from cells of the neurovascular unit, with brain amyloid-ß deposition in menopausal women. METHODS: A subset of women from the Kronos Early Estrogen Prevention Study underwent brain amyloid-ß positron emission tomography three years following cessation of study treatment with placebo (PL, n = 29), transdermal 17ß-estradiol (tE2; n = 21), or oral conjugated equine estrogen (oCEE; n = 17). Isolated peripheral venous blood microvesicles were analyzed by digital flow cytometry using fluorophore conjugated antibodies directed toward total tau, amyloid-ß 1-42 (Aß1-42), neuron specific class III ß-tubulin (Tuj1), microglia ionized calcium -binding adaptor molecule 1(Iba1), glial fibrillary acid protein (GFAP), and low density lipoprotein receptor-related protein1 (LRP1). Principal components analysis reduced the dimensionality of these selected six markers to two principal components (PCs). Proportional odds ordinal logistic regression analysis was used with amyloid-ß deposition regressed on these PCs. RESULTS: Only the number of microvesicles positive for Aß1-42 differed statistically among prior treatment groups (median [IQR] 6.06 [2.11, 12.55] in PL; 2.49 [0.73, 3.59] in tE2; and 4.96 [0.83, 10.31] in oCEE; p = 0.032). The joint association between the 2 PCs and brain amyloid-ß deposition was significant (p = 0.045). CONCLUSION: Six selected markers expressing peripheral blood microvesicles derived from cells of the neurovascular unit, when summarized into two principal components, were associated with brain amyloid-ß deposition.