title: 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.
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Saila
authors.initials: S
authors.lastname: Vepsäläinen
authors.forename: Henna
authors.initials: H
authors.lastname: Koivisto
authors.forename: Elina
authors.initials: E
authors.lastname: Pekkarinen
authors.forename: Petra
authors.initials: P
authors.lastname: Mäkinen
authors.forename: Gary
authors.initials: G
authors.lastname: Dobson
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: McDougall
authors.forename: Derek
authors.initials: D
authors.lastname: Stewart
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.forename: Reijo O
authors.initials: RO
authors.lastname: Karjalainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010936:Plant Extracts / Q000494:pharmacology*; D053764:Presenilin-1 / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D031965:Ribes / Q000737:chemistry*; D029800:Vaccinium myrtillus / Q000737:chemistry*; D024483:Vitamin K 3 / Q000633:toxicity; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D000872:Anthocyanins; D005419:Flavonoids; C558298:Mapt protein, mouse; D010936:Plant Extracts; D053764:Presenilin-1; D017382:Reactive Oxygen Species; D016875:tau Proteins; D024483:Vitamin K 3; C040015:myricetin; D011794:Quercetin; D053829:Amyloid Precursor Protein Secretases