Anti- N-homocysteine-protein autoantibodies are associated with impaired cognition

Olga Włoczkowska; Joanna Perła-Kaján; A David Smith; Celeste de Jager; Helga Refsum; Hieronim Jakubowski

doi:10.1002/trc2.12159

Anti- N-homocysteine-protein autoantibodies are associated with impaired cognition

Alzheimers Dement (N Y). 2021 Mar 31;7(1):e12159. doi: 10.1002/trc2.12159. eCollection 2021.

Authors

Olga Włoczkowska¹, Joanna Perła-Kaján¹, A David Smith², Celeste de Jager², Helga Refsum³, Hieronim Jakubowski^{1

4}

Affiliations

¹ Department of Biochemistry and Biotechnology Poznań University of Life Sciences Poznań Poland.
² OPTIMA Department of Pharmacology University of Oxford Oxford UK.
³ Department of Nutrition Institute of Basic Medical Sciences University of Oslo Oslo Norway.
⁴ Department of Microbiology Biochemistry and Molecular Genetics New Jersey Medical School International Center for Public Health Rutgers University Newark New Jersey USA.

Abstract

Introduction: Elevated homocysteine (Hcy) and related metabolites accelerate Alzheimer's disease. Hcy-lowering B vitamins slow brain atrophy/cognitive decline in mild cognitive impairment (MCI). Modification with Hcy-thiolactone generates auto-immunogenic N-Hcy-protein. We tested a hypothesis that anti-N-Hcy-protein autoantibodies predict cognition in individuals with MCI participating in a randomized, double-blind, placebo-controlled VITACOG trial of B vitamins.

Methods: Participants with MCI (n = 196, 76.8 years old, 60% women) were randomly assigned to receive a daily dose of folic acid (0.8 mg), vitamin B₁₂ (0.5 mg), and B₆ (20 mg) (n = 98) or placebo (n = 98) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of patients (n = 167) by magnetic resonance imaging. Anti N-Hcy-protein auto-antibodies were quantified by enzyme-linked immunosorbent assay. Associations among anti-N-Hcy-protein autoantibodies, cognition, and brain atrophy were examined by multiple regression analysis.

Results: At baseline, anti-N-Hcy-protein autoantibodies were significantly associated with impaired global cognition (Mini-Mental State Examination [MMSE]), episodic memory (Hopkins Verbal Learning Test-revised), and attention/processing speed (Map Search). At the end of the study, anti-N-Hcy-protein autoantibodies were associated with impaired global cognition (MMSE) and attention/processing speed (Trail Making A). In the placebo group, baseline anti-N-Hcy-protein autoantibodies predicted, independently of Hcy, global cognition (Telephone Inventory for Cognitive Status modified [TICS-m]; MMSE) and attention/processing speed (Trail Making A) but not brain atrophy, at the end of study. B-vitamin treatment abrogated association of anti-N-Hcy-protein autoantibodies with cognition.

Discussion: These findings suggest that anti-N-Hcy-protein autoantibodies can impair functional (attention/processing speed and global cognition), but not structural (brain atrophy), aspects of cognition. Anti-N-Hcy-protein autoantibodies are a new factor associated with impaired cognition, which could be ameliorated by B vitamins.

Keywords: anti‐N‐Hcy‐protein autoantibodies; brain atrophy; cognition; homocysteine; mild cognitive impairment.