Brain γ-Tocopherol Levels Are Associated with Presynaptic Protein Levels in Elderly Human Midfrontal Cortex.

Abstract

BACKGROUND:

Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation.

OBJECTIVE:

In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans.

METHODS:

We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels.

RESULTS:

Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer's disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels.

CONCLUSION:

In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.

• Authors: Francisca A de Leeuw, William G Honer, Julie A Schneider, Martha Clare Morris
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 77 Issue 2 Pg. 619-627 ( 2020) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 32741813 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• gamma-Tocopherol

Topics

• Aged
• Aged, 80 and over
• Cross-Sectional Studies
• Female
• Frontal Lobe (drug effects, metabolism, pathology)
• Humans
• Male
• Membrane Proteins (metabolism)
• Presynaptic Terminals (drug effects, metabolism, pathology)
• Single-Blind Method
• Surveys and Questionnaires
• gamma-Tocopherol (administration & dosage, metabolism)