Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, affecting over 55 million people worldwide. Histopathological hallmarks of this multifactorial disease are an increased plaque burden and tangles in the brains of affected individuals. Several lines of evidence indicate that B12 hypovitaminosis is linked to AD. In this review, the biochemical pathways involved in AD that are affected by vitamin B12, focusing on APP processing, Aβ fibrillization, Aβ-induced oxidative damage as well as tau hyperphosphorylation and tau aggregation, are summarized. Besides the mechanistic link, an overview of clinical studies utilizing vitamin B supplementation are given, and a potential link between diseases and medication resulting in a reduced vitamin B12 level and AD are discussed. Besides the disease-mediated B12 hypovitaminosis, the reduction in vitamin B12 levels caused by an increasing change in dietary preferences has been gaining in relevance. In particular, vegetarian and vegan diets are associated with vitamin B12 deficiency, and therefore might have potential implications for AD. In conclusion, our review emphasizes the important role of vitamin B12 in AD, which is particularly important, as even in industrialized countries a large proportion of the population might not be sufficiently supplied with vitamin B12.

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

“…Factors such as elevated inflammatory markers have been associated with increased adipose tissue levels ( Aguilar-Valles et al, 2015 , Miller and Spencer, 2014 ), even specifically during the menopause transition ( Lee et al, 2009 ), as well as decreasing oestrogens ( McCarthy and Raval, 2020 ), brain atrophy ( Luo et al, 2022 ), and dementia risk ( Heneka et al, 2015 , Ransohoff, 2016 ). Biological markers of obesity, such as lipid profile ( Anstey et al, 2017 , Reitz, 2012 ), glucose ( Crane et al, 2013 ), HbA1c ( Ramirez et al, 2015 ), leptin ( Zeki Al Hazzouri et al, 2013 ), and Vitamin B12 ( Lauer et al, 2022 ), may also influence associations between adipose tissue and brain health, and contribute to risk of comorbidities such as type II diabetes and hypertension, which are known to impact neural and cardiometabolic health ( Cole, 2020 , Fuchs and Whelton, 2020 , Newby et al, 2022 , Peters et al, 2014 ).…”

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

“…The protective effect of vitamin B12 in respect to tau hyperphosphorylation and tau aggregation is reported to be caused by an elevation in the activity of the phospholipase A2 [ 145 ], an inhibition of kinases involved in tau phosphorylation e.g., GSK-3β [ 146 ], and by the direct binding of vitamin B12 to tau proteins [ 147 ]. In line with the obtained and discussed positive properties of vitamin B12 in respect to the lipid alterations found in AD, several clinical randomized controlled trials with patients affected by mild cognitive impairment or AD have already revealed the beneficial effects of vitamin B12 when used alone or in combination with vitamin B6 or folic acid [ 115 ]. These results further underline the therapeutic potential of vitamin B12 to treat or prevent AD.…”

“…Potential explanations for the observed lipid changes and potential beneficial properties of vitamin B12 in respect to AD are given in the Supplementary Discussion as further background information. However, these explanations are based on literature and should not be overinterpreted without further experimental proof [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ].…”

Dietary and Nutrient Patterns and Brain MRI Biomarkers in Dementia-Free Adults

“…Collectively, these findings suggest that the high intake of specific nutrients, such as unsaturated fatty acids (PUFAs, MUFAs), fibers, vitamin E, vitamin D and flavonoids, may be implicated in the relationships. It should be noted, however, that the mechanisms through which vitamins and unsaturated fatty acids may exert their protective effects may be completely different; vitamins may exert their role through oxidation and effects in total brain atrophy, whereas unsaturated fatty acids through vascular mechanisms [ 58 , 59 , 60 ]. Further research is needed for the confirmation of the hypotheses and the clarification of the mechanisms.…”