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Review
. 2022 Jan 14;12(1):129.
doi: 10.3390/biom12010129.

Mechanistic Link between Vitamin B12 and Alzheimer's Disease

Anna Andrea Lauer  1 , Heike Sabine Grimm  1 , Birgit Apel  2 , Nataliya Golobrodska  2 , Lara Kruse  2 , Elina Ratanski  2 , Noemi Schulten  2 , Laura Schwarze  2 , Thomas Slawik  2 , Saskia Sperlich  2 , Antonia Vohla  2 , Marcus Otto Walter Grimm  1   2   3
Affiliations
Review

Mechanistic Link between Vitamin B12 and Alzheimer's Disease

Anna Andrea Lauer et al. Biomolecules. .

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.

Keywords: Alzheimer’s disease; Amyloid beta; cobalamin; homocysteine; intrinsic factor; tau pathology; vegan diet; vegetarian diet; vitamin B12.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview of amyloidogenic and non-amyloidogenic APP processing and generated cleavage products.
Figure 2
Figure 2
Stylized illustration of the homocysteine/methionine cycle and biochemical mechanism of action of vitamin B12 in the homocysteine/methionine and the methyl-malonyl-CoA pathway. The complex Kennedy pathway involved in phosphatidylcholine synthesis is not illustrated in detail. PtDEth: phosphatidylethanolamine; PtDCh: phosphatidylcholine; SAM: s-adenosyl-methionine; SAH: s-adenosyl-homocysteine.
Figure 3
Figure 3
Summary of the proposed beneficial properties of vitamin B12 with respect to amyloid and tau pathology in AD based on the discussed cell culture, in vitro and animal studies. In this context it has to be mentioned that some of the illustrated potential mechanisms (marked with asterisks) are based on studies under vitamin B12 (and folate) deficiency/hypovitaminosis.
See this image and copyright information in PMC

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