A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice

L M. Broersen, A.A.M. Kuipers, M. Balvers, N. van Wijk, Paul H.M. Savelkoul, M.C. de Wilde, E.M. van der Beek, J.W.C. Sijben, R.J.J. Hageman, P. Kamphuis, A. J. Kiliaan

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Diet is an important lifestyle factor implicated in the etiology of Alzheimer's disease (AD), but so far it is not fully elucidated to which nutrients the suggested protective effect of diet can be attributed. Recent evidence obtained in the amyloid-beta 1-42 (A beta(42)) infusion model in rats has shown that a multi-nutrient intervention known as Fortasyn (TM) Connect (FC) may protect the central cholinergic system against A beta(42)-induced toxicity. FC comprises the nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid (DHA), eicosapentaenoic acid, uridine-mono-phosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium. In order to investigate whether the combined administration of these nutrients may also affect AD-like pathology, we now evaluated the effects of the FC diet intervention in the transgenic A beta PPswe/PS1(dE9) mouse model with endogenous A beta production. In addition we evaluated the effects of diets containing the individual nutrients DHA and UMP and their combination in this model. Between the age of 3 and 6 months, FC diet decreased brain A beta levels and amyloid plaque burden in the hippocampus of A beta PP/PS1 mice. The FC diet also reduced ongoing disintegrative degeneration in the neocortex, as indicated by Amino Cupric Silver staining. Although all three DHA-containing diets were equally effective in changing brain fatty acid profiles, diets differentially affected amyloid-related measures, indicating that effects of DHA may depend on its dietary context. The current data, showing that dietary enrichment with FC reduces AD-like pathology in A beta PP/PS1 mice, confirm and extend our previous findings in the A beta(42) infusion model and favor the combined administration of relevant nutrients.
Original languageEnglish
Pages (from-to)177-190
JournalJournal of Alzheimer's Disease
Volume33
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013

Cite this

Broersen, L M. ; Kuipers, A.A.M. ; Balvers, M. ; van Wijk, N. ; Savelkoul, Paul H.M. ; de Wilde, M.C. ; van der Beek, E.M. ; Sijben, J.W.C. ; Hageman, R.J.J. ; Kamphuis, P. ; Kiliaan, A. J. / A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice. In: Journal of Alzheimer's Disease. 2013 ; Vol. 33, No. 1. pp. 177-190.
@article{a4ffa5e2f4de409692c6ca6bd3fa3180,
title = "A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice",
abstract = "Diet is an important lifestyle factor implicated in the etiology of Alzheimer's disease (AD), but so far it is not fully elucidated to which nutrients the suggested protective effect of diet can be attributed. Recent evidence obtained in the amyloid-beta 1-42 (A beta(42)) infusion model in rats has shown that a multi-nutrient intervention known as Fortasyn (TM) Connect (FC) may protect the central cholinergic system against A beta(42)-induced toxicity. FC comprises the nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid (DHA), eicosapentaenoic acid, uridine-mono-phosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium. In order to investigate whether the combined administration of these nutrients may also affect AD-like pathology, we now evaluated the effects of the FC diet intervention in the transgenic A beta PPswe/PS1(dE9) mouse model with endogenous A beta production. In addition we evaluated the effects of diets containing the individual nutrients DHA and UMP and their combination in this model. Between the age of 3 and 6 months, FC diet decreased brain A beta levels and amyloid plaque burden in the hippocampus of A beta PP/PS1 mice. The FC diet also reduced ongoing disintegrative degeneration in the neocortex, as indicated by Amino Cupric Silver staining. Although all three DHA-containing diets were equally effective in changing brain fatty acid profiles, diets differentially affected amyloid-related measures, indicating that effects of DHA may depend on its dietary context. The current data, showing that dietary enrichment with FC reduces AD-like pathology in A beta PP/PS1 mice, confirm and extend our previous findings in the A beta(42) infusion model and favor the combined administration of relevant nutrients.",
author = "Broersen, {L M.} and A.A.M. Kuipers and M. Balvers and {van Wijk}, N. and Savelkoul, {Paul H.M.} and {de Wilde}, M.C. and {van der Beek}, E.M. and J.W.C. Sijben and R.J.J. Hageman and P. Kamphuis and Kiliaan, {A. J.}",
year = "2013",
month = "1",
day = "1",
doi = "10.3233/JAD-2012-112039",
language = "English",
volume = "33",
pages = "177--190",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

Broersen, LM, Kuipers, AAM, Balvers, M, van Wijk, N, Savelkoul, PHM, de Wilde, MC, van der Beek, EM, Sijben, JWC, Hageman, RJJ, Kamphuis, P & Kiliaan, AJ 2013, 'A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice', Journal of Alzheimer's Disease, vol. 33, no. 1, pp. 177-190. https://doi.org/10.3233/JAD-2012-112039

A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice. / Broersen, L M.; Kuipers, A.A.M.; Balvers, M.; van Wijk, N.; Savelkoul, Paul H.M.; de Wilde, M.C.; van der Beek, E.M.; Sijben, J.W.C.; Hageman, R.J.J.; Kamphuis, P.; Kiliaan, A. J.

In: Journal of Alzheimer's Disease, Vol. 33, No. 1, 01.01.2013, p. 177-190.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult A beta PPswe/PS1(dE9) Mice

AU - Broersen, L M.

AU - Kuipers, A.A.M.

AU - Balvers, M.

AU - van Wijk, N.

AU - Savelkoul, Paul H.M.

AU - de Wilde, M.C.

AU - van der Beek, E.M.

AU - Sijben, J.W.C.

AU - Hageman, R.J.J.

AU - Kamphuis, P.

AU - Kiliaan, A. J.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Diet is an important lifestyle factor implicated in the etiology of Alzheimer's disease (AD), but so far it is not fully elucidated to which nutrients the suggested protective effect of diet can be attributed. Recent evidence obtained in the amyloid-beta 1-42 (A beta(42)) infusion model in rats has shown that a multi-nutrient intervention known as Fortasyn (TM) Connect (FC) may protect the central cholinergic system against A beta(42)-induced toxicity. FC comprises the nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid (DHA), eicosapentaenoic acid, uridine-mono-phosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium. In order to investigate whether the combined administration of these nutrients may also affect AD-like pathology, we now evaluated the effects of the FC diet intervention in the transgenic A beta PPswe/PS1(dE9) mouse model with endogenous A beta production. In addition we evaluated the effects of diets containing the individual nutrients DHA and UMP and their combination in this model. Between the age of 3 and 6 months, FC diet decreased brain A beta levels and amyloid plaque burden in the hippocampus of A beta PP/PS1 mice. The FC diet also reduced ongoing disintegrative degeneration in the neocortex, as indicated by Amino Cupric Silver staining. Although all three DHA-containing diets were equally effective in changing brain fatty acid profiles, diets differentially affected amyloid-related measures, indicating that effects of DHA may depend on its dietary context. The current data, showing that dietary enrichment with FC reduces AD-like pathology in A beta PP/PS1 mice, confirm and extend our previous findings in the A beta(42) infusion model and favor the combined administration of relevant nutrients.

AB - Diet is an important lifestyle factor implicated in the etiology of Alzheimer's disease (AD), but so far it is not fully elucidated to which nutrients the suggested protective effect of diet can be attributed. Recent evidence obtained in the amyloid-beta 1-42 (A beta(42)) infusion model in rats has shown that a multi-nutrient intervention known as Fortasyn (TM) Connect (FC) may protect the central cholinergic system against A beta(42)-induced toxicity. FC comprises the nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid (DHA), eicosapentaenoic acid, uridine-mono-phosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium. In order to investigate whether the combined administration of these nutrients may also affect AD-like pathology, we now evaluated the effects of the FC diet intervention in the transgenic A beta PPswe/PS1(dE9) mouse model with endogenous A beta production. In addition we evaluated the effects of diets containing the individual nutrients DHA and UMP and their combination in this model. Between the age of 3 and 6 months, FC diet decreased brain A beta levels and amyloid plaque burden in the hippocampus of A beta PP/PS1 mice. The FC diet also reduced ongoing disintegrative degeneration in the neocortex, as indicated by Amino Cupric Silver staining. Although all three DHA-containing diets were equally effective in changing brain fatty acid profiles, diets differentially affected amyloid-related measures, indicating that effects of DHA may depend on its dietary context. The current data, showing that dietary enrichment with FC reduces AD-like pathology in A beta PP/PS1 mice, confirm and extend our previous findings in the A beta(42) infusion model and favor the combined administration of relevant nutrients.

U2 - 10.3233/JAD-2012-112039

DO - 10.3233/JAD-2012-112039

M3 - Article

VL - 33

SP - 177

EP - 190

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -