Brain tocopherols related to Alzheimer's disease neuropathology in humans

Randomized trials of alpha-tocopherol supplements on cognitive decline are negative, whereas studies of dietary tocopherols have shown benefit. We investigated these inconsistencies by analyzing the relations of alpha- and gamma-tocopherol brain concentrations to Alzheimer's disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adjusted linear regression models. gamma-Tocopherol concentrations were associated with lower amyloid load (beta = -2.10, P = .002) and lower neurofibrillary tangle severity (beta = -1.16, P = .02). Concentrations of alpha-tocopherol were not associated with AD neuropathology, except as modified by gamma-tocopherol: high. alpha-tocopherol was associated with higher amyloid load when -gamma-tocopherol levels were low and with lower amyloid levels when gamma-tocopherol levels were high (P for interaction = 0.03). Brain concentrations of gamma- and alpha-tocopherols may be associated with AD neuropathology in interrelated, complex ways. Randomized trials should consider the contribution of gamma-tocopherol. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.