Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid precursor protein processing and alleviate behavioral abnormalities in the APP/PS1 mouse model of Alzheimer’s disease
Abstract
A growing body of epidemiological evidence suggests that fruit and vegetable juices containing various phenolic compounds can reduce the risk of Alzheimer's disease (AD). As the altered amyloid precursor protein (APP) processing leading to increased β-amyloid (Aβ) production is a key pathogenic feature of AD, we elucidated the effects of different polyphenols on neuroprotection and APP processing under different in vitro stress conditions. The effects of these compounds were also investigated in transgenic AD mice (APdE9). Free radical toxicity and apoptosis were induced in human SH-SY5Y neuroblastoma cells overexpressing APP751. Menadione-induced production of reactive oxygen species was significantly decreased upon treatment with myricetin, quercetin or anthocyanin-rich extracts in a dose-dependent manner. However, these extracts did not affect caspase-3 activation, APP processing or Aβ levels upon staurosporine-induced apoptosis. APdE9 mice fed with anthocyanin-rich bilberry or blackcurrant extracts showed decreased APP C-terminal fragment levels in the cerebral cortex as compared to APdE9 mice on the control diet. Soluble Aβ40 and Aβ42 levels were significantly decreased in bilberry-fed mice as compared to blackcurrant-fed mice. Conversely, the ratio of insoluble Aβ42/40 was significantly decreased in blackcurrant-fed mice relative to bilberry-fed mice. Both berry diets alleviated the spatial working memory deficit of aged APdE9 mice as compared to mice on the control diet. There were no changes in the expression or phosphorylation status of tau in APdE9 mice with respect to diet. These data suggest that anthocyanin-rich bilberry and blackcurrant diets favorably modulate APP processing and alleviate behavioral abnormalities in a mouse model of AD.
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Treatments with either total anthocyanins extracted from bilberry and black currant or isolated cyanidin-3-O-glucopyranoside were able to ameliorate cognitive functions in APP/PS1 mice.
“Treatments with either total anthocyanins extracted from bilberry and black currant [106] or isolated cyanidin-3-O-glucopyranoside, which is the predominant anthocyanin in colored fruit and vegetables [107], were able to ameliorate cognitive functions in APP/PS1 mice.”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [106]
The beneficial cognitive effects of anthocyanins are related, at least in part, to the improvement in processing of beta amyloid and neuroinflammation, which follows the activation of PPARγ.
“As summarized in Figure 2, the beneficial cognitive effects of anthocyanins are related, at least in part, to the improvement in processing of beta amyloid and neuroinflammation, which follows the activation of peroxisome proliferator-activated receptor γ (PPARγ) [106].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [106]
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- Authors
- Vepsäläinen, S., Koivisto, H., Pekkarinen, E., Mäkinen, P., Dobson, G., McDougall, G. J., Stewart, D., Haapasalo, A., Karjalainen, R. O., Tanila, H., & Hiltunen, M.
- Affiliations
- University of Eastern Finland (FI)
- James Hutton Institute (GB)
- Corresponding author
- Hiltunen, Mikko
- ORCID
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 24
- Issue
- 1
- Pages
- 360-370
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2148945876
- Cited by
- 150
- References
- 37
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 15 · 2021: 15 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 15 · 2013: 4
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- anthocyanins, Vaccinium myrtillus, black currant, Alzheimer's disease, APP processing, APP/PS1 mice, amyloid-beta, myricetin, quercetin, reactive oxygen species, neuroprotection, spatial working memory, dietary polyphenols, tau phosphorylation
- MeSH terms
- Alzheimer Disease, Animals, Anthocyanins, Behavior, Animal, Brain, Cell Line, Disease Models, Animal, Flavonoids, Humans, Male, Memory, Short-Term, Mice, Transgenic, Plant Extracts, Quercetin, Amyloid beta-Protein Precursor, tau Proteins, Reactive Oxygen Species, Vitamin K 3, Vaccinium myrtillus, Ribes, Mice, Presenilin-1, Amyloid Precursor Protein Secretases
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