Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer's Disease

Abstract

Background: Oxidative stress contributes to pathogenesis and progression of Alzheimer's disease (AD). Higher levels of the dietary antioxidants- carotenoids and tocopherols- are associated with better cognitive functions and lower risk for AD, and lower levels of multiple carotenoids are found in serum and plasma of patients with AD. Although brains donated by individuals with mild cognitive impairment had significantly lower levels of lutein and beta-carotene, previous investigators found no significant difference in carotenoid levels of brains with AD and cognitively normal brains.

Objective: This study tested the hypothesis that micronutrients are significantly lower in donor brains with AD than in healthy elderly brains.

Methods: Samples of donor brains with confirmed AD or verified health were dissected into grey and white matter, extracted with organic solvents and analyzed by HPLC.

Results: AD brains had significantly lower levels of lutein, zeaxanthin, anhydrolutein, retinol, lycopene, and alpha-tocopherol, and significantly increased levels of XMiAD, an unidentified xanthophyll metabolite. No meso-zeaxanthin was detected. The overlapping protective roles of xanthophylls, carotenes, α- and γ-tocopherol are discussed.

Conclusion: Brains with AD had substantially lower concentrations of some, but not all, xanthophylls, carotenes, and tocopherols, and several-fold higher concentrations of an unidentified xanthophyll metabolite increased in AD (XMiAD).

Keywords: Alzheimer’s disease; antioxidants; brain; carotenoids; deficiency; lutein; lycopene; meso-zeaxanthin; oxidation; tocopherols; zeaxanthin.

Fig. 1

Mean concentrations (+S.E.) of xanthophylls and carotenes (A), retinol, and tocopherols (B) in HE and AD brains from (light and dark bars, respectively). B) Note different axis and that α-tocopherol and γ-tocopherol are represented as 1/100 and 1/5 their actual concentration. Significant differences between HE and AD determined by ANOVA: ^#p = 0.07–0.09; ^*p = 0.02–0.05; ^***p = 0.002–0.004.

Fig. 2

A) Lutein and zeaxanthin concentrations in grey and white matter of HE and AD brains. In AD brains, lutein exceeded zeaxanthin (* above bars); zeaxanthin in grey matter was lower in AD than in HE brains (*in bars). B) Mean L:Z ratio in AD and HE brains. ^*p = 0.02–0.05; ^***p = 0.002; ^****p = 0.00002

Fig. 3

Separation of zeaxanthin optical isomers in a racemic mixture and in the brain zeaxanthin fraction collected during normal phase LC. Brain contained only the 3R, 3’R enantiomer of zeaxanthin.

Fig. 4

Mean % HE (+S.E.) illustrates relative analyte deficits in AD grey and white matter (dark and light bars, respectively). Asterisks above the bar identify analytes whose % HE in AD brains was significantly below those in HE brains (dashed line); γ-tocopherol was significantly lower only in grey matter (asterisk in the bar). ^*p = 0.02–0.05; ^***p = 0.001–0.004

Fig. 5

A) XMiAD concentration (mean + S.E.) in grey and white matter (dark and light bars, respectively) of HE and AD brains (p = 0.002; ANOVA). B) Relative to HE brains, the fold-increase of XMiAD in AD was greater in grey matter than in white matter (p = 0.007).

Fig. 6

Negative correlation of XMiAD with age of AD brain donors in both grey and white matter (dark and light markers, respectively).