PMID- 34737043
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20221202
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 161
DP  - 2021 Dec
TI  - Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: 
      Evidence from clinicopathological and preclinical studies.
PG  - 105542
LID - S0969-9961(21)00291-6 [pii]
LID - 10.1016/j.nbd.2021.105542 [doi]
AB  - BACKGROUND: Vitamin A (VitA), via its active metabolite retinoic acid (RA), is 
      critical for the maintenance of memory function with advancing age. Although its 
      role in Alzheimer's disease (AD) is not well understood, data suggest that 
      impaired brain VitA signaling is associated with the accumulation of beta-amyloid 
      peptides (Abeta), and could thus contribute to the onset of AD. METHODS: We 
      evaluated the protective action of a six-month-long dietary VitA-supplementation 
      (20 IU/g), starting at 8 months of age, on the memory and the neuropathology of 
      the 3xTg-AD mouse model of AD (n = 11-14/group; including 4-6 females and 7-8 
      males). We also measured protein levels of Retinoic Acid Receptor beta (RARbeta) and 
      Retinoid X Receptor gamma (RXRgamma) in homogenates from the inferior parietal cortex of 
      60 participants of the Religious Orders study (ROS) divided in three groups: no 
      cognitive impairment (NCI) (n = 20), mild cognitive impairment (MCI) (n = 20) and 
      AD (n = 20). RESULTS: The VitA-enriched diet preserved spatial memory of 3xTg-AD 
      mice in the Y maze. VitA-supplementation affected hippocampal RXR expression in 
      an opposite way according to sex by tending to increase in males and decrease in 
      females their mRNA expression. VitA-enriched diet also reduced the amount of 
      hippocampal Abeta(40) and Abeta(42), as well as the phosphorylation of tau protein at 
      sites Ser396/Ser404 (PHF-1) in males. VitA-supplementation had no effect on tau 
      phosphorylation in females but worsened their hippocampal Abeta load. However, the 
      expression of Rxr-beta in the hippocampus was negatively correlated with the amount 
      of both soluble and insoluble Abeta in both males and females. Western 
      immunoblotting in the human cortical samples of the ROS study did not reveal 
      differences in RARbeta levels. However, it evidenced a switch from a 60-kDa-RXRgamma to 
      a 55-kDa-RXRgamma in AD, correlating with ante mortem cognitive decline and the 
      accumulation of neuritic plaques in the brain cortex. CONCLUSION: Our data 
      suggest that (i) an altered expression of RXRs receptors is a contributor to 
      beta-amyloid pathology in both humans and 3xTg-AD mice, (ii) a chronic exposure of 
      3xTg-AD mice to a VitA-enriched diet may be protective in males, but not in 
      females.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Biyong, Essi F
AU  - Biyong EF
AD  - Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, 
      France; Faculte de pharmacie, Universite Laval, Quebec, Quebec, Canada; Centre de 
      recherche du CHU de Quebec-Universite Laval (CHUL), Axe Neurosciences, 2705 
      Boulevard Laurier, Quebec, Quebec, Canada; Institut sur la Nutrition et les 
      Aliments Fonctionnels (INAF), Quebec, Quebec, Canada; LIA OptiNutriBrain - 
      Laboratoire International Associe (NutriNeuro France-INAF Canada), Canada.
FAU - Tremblay, Cyntia
AU  - Tremblay C
AD  - Faculte de pharmacie, Universite Laval, Quebec, Quebec, Canada; Centre de 
      recherche du CHU de Quebec-Universite Laval (CHUL), Axe Neurosciences, 2705 
      Boulevard Laurier, Quebec, Quebec, Canada.
FAU - Leclerc, Manon
AU  - Leclerc M
AD  - Faculte de pharmacie, Universite Laval, Quebec, Quebec, Canada; Centre de 
      recherche du CHU de Quebec-Universite Laval (CHUL), Axe Neurosciences, 2705 
      Boulevard Laurier, Quebec, Quebec, Canada.
FAU - Caron, Vicky
AU  - Caron V
AD  - Faculte de pharmacie, Universite Laval, Quebec, Quebec, Canada; Centre de 
      recherche du CHU de Quebec-Universite Laval (CHUL), Axe Neurosciences, 2705 
      Boulevard Laurier, Quebec, Quebec, Canada.
FAU - Alfos, Serge
AU  - Alfos S
AD  - Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, 
      France.
FAU - Helbling, Jean-Christophe
AU  - Helbling JC
AD  - Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, 
      France.
FAU - Rodriguez, Lea
AU  - Rodriguez L
AD  - CUO-Recherche, Centre de Recherche du CHU de Quebec, Quebec, QC, Canada; 
      Departement d'ophtalmologie, Faculte de Medecine, Universite Laval, Quebec, QC, 
      Canada.
FAU - Pernet, Vincent
AU  - Pernet V
AD  - CUO-Recherche, Centre de Recherche du CHU de Quebec, Quebec, QC, Canada; 
      Departement d'ophtalmologie, Faculte de Medecine, Universite Laval, Quebec, QC, 
      Canada.
FAU - Bennett, David A
AU  - Bennett DA
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 
      USA.
FAU - Pallet, Veronique
AU  - Pallet V
AD  - Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, 
      France; LIA OptiNutriBrain - Laboratoire International Associe (NutriNeuro 
      France-INAF Canada), Canada.
FAU - Calon, Frederic
AU  - Calon F
AD  - Faculte de pharmacie, Universite Laval, Quebec, Quebec, Canada; Centre de 
      recherche du CHU de Quebec-Universite Laval (CHUL), Axe Neurosciences, 2705 
      Boulevard Laurier, Quebec, Quebec, Canada; Institut sur la Nutrition et les 
      Aliments Fonctionnels (INAF), Quebec, Quebec, Canada; LIA OptiNutriBrain - 
      Laboratoire International Associe (NutriNeuro France-INAF Canada), Canada. 
      Electronic address: frederic.calon@crchudequebec.ulaval.ca.
LA  - eng
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - RF1 AG015819/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211101
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (tau Proteins)
RN  - 11103-57-4 (Vitamin A)
SB  - IM
MH  - *Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Diet
MH  - Disease Models, Animal
MH  - Female
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Retinoid X Receptors/metabolism
MH  - *Vitamin A
MH  - tau Proteins/metabolism
PMC - PMC8649044
MID - NIHMS1756279
OTO - NOTNLM
OT  - 3xTg-AD mouse
OT  - Aging
OT  - Alzheimer's disease
OT  - Amyloid
OT  - Diet
OT  - Prevention
OT  - RXRs
OT  - Sex
OT  - Vitamin A
COIS- Competing interests The authors declare that they have no competing interests.
EDAT- 2021/11/06 06:00
MHDA- 2022/04/08 06:00
PMCR- 2022/12/01
CRDT- 2021/11/05 05:49
PHST- 2020/12/07 00:00 [received]
PHST- 2021/10/27 00:00 [revised]
PHST- 2021/10/31 00:00 [accepted]
PHST- 2021/11/06 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/11/05 05:49 [entrez]
PHST- 2022/12/01 00:00 [pmc-release]
AID - S0969-9961(21)00291-6 [pii]
AID - 10.1016/j.nbd.2021.105542 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2021 Dec;161:105542. doi: 10.1016/j.nbd.2021.105542. Epub 2021 Nov 
      1.