Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease
Molecular Neurodegeneration Vol 11, Article number: 22 (2016) https://doi.org/10.1186/s13024-016-0087-2
Véréna Landel, Pascal Millet, Kévin Baranger, Béatrice Loriod & François Féron
- Alzheimer’s is associated with all 7 of the genes which restrict vitamin D from getting to tissues – Sept 2018
- Lower vitamin D in blood causes Alzheimer's Disease (Mendelian gene analysis) – Dec 2019
Overview Alzheimer's-Cognition and Vitamin D starts with:
- FACT: Cognitive decline is 19X more likely if low vitamin D
- FACT: Dementia is associated with low vitamin D levels.
- FACT: Alzheimer’s Dementia 2.3X more likely in elderly if low vitamin D – Dec 2022
- FACT: Dementia is associated with low vitamin D - many studies
- FACT: Alzheimer's Disease is 4X less likely if high vitamin D
- FACT: Every single risk factor listed for Alzheimer's Disease is also a risk factor for low vitamin D levels
- FACT: Elderly cognition gets worse as the elderly vitamin D levels get even lower (while in senior homes)
- OBSERVATION: Reports of increased vitamin D levels result in improved cognition
- OBSERVATION: Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012
- OBSERVATION: Alzheimer's Disease has been seen to halt when vitamin D was added.
- OBSERVATION: Alzheimer’s is associated with all 7 of the genes which restrict vitamin D
- OBSERVATION: 39 vitamin D and Alz. or Cognition intervention trials as of Sept 2018
- OBSERVATION: 2 Meta-analysis in 2012 agreed that Alzheimer's Disease. associated with low vitamin D
- OBSERVATION: 50X increase in Alzheimer's while decrease in vitamin D
- OBSERVATION: Vitamin D reduces Alzheimer’s disease in 11 ways
- OBSERVATION: Alzheimer’s cognition improved by 4,000 IU of vitamin D
- OBSERVATION: Plaque removed in mice by equiv. of 14,000 IU daily
- OBSERVATION: DDT (which decreases Vit D) increases risk of Alzheimer's by up to 3.8X
- OBSERVATION: 2% of people have 2 copies of the poor gene reference: Alz Org
- OBSERVATION: Genes do not change rapidly enough to account for the huge increase in incidence
- OBSERVATION: End of Alzheimer's videos, transcripts and many studies protocol has been very successful
- It adjusts Vitamin D, B-12, Iron, Omega-3, food, etc, and can now be done at home.
- FACT: Vitamin D is extremely low cost and has very very few side effects
- CONCLUSION: Everyone concerned about cognitive decline or Alzheimer's Disease should take vitamin D
- PREDICTION MET: By 2024 Omega-3 and high dose Vitamin D will be found to reverse Alzheimer's in humans
There are 13+ Alzheimer’s meta-analyses in VitaminDWiki
There are 97+ Alzheimer’s studies in VitaminDWiki
Dementia is associated with low vitamin D - many studies 50+ studies
16+ studies in both categories Cognitive and Omega-3
Download the PDF from VitaminDWiki
Background
Increasing evidence suggests a potential therapeutic benefit of vitamin D supplementation against Alzheimer’s disease (AD). Although studies have shown improvements in cognitive performance and decreases in markers of the pathology after chronic treatment, the mechanisms by which vitamin D acts on brain cells are multiple and remain to be thoroughly studied. We analyzed the molecular changes observed after 5 months of vitamin D3 supplementation in the brains of transgenic 5xFAD (Tg) mice, a recognized mouse model of AD, and their wild type (Wt) littermates. We first performed a kinematic behavioural examination at 4, 6 and 8 months of age (M4, M6 and M8) followed by a histologic assessment of AD markers. We then performed a comparative transcriptomic analysis of mRNA regulation in the neocortex and hippocampus of 9 months old (M9) female mice.
Results
Transcriptomic analysis of the hippocampus and neocortex of both Wt and Tg mice at M9, following 5 months of vitamin D3 treatment, reveals a large panel of dysregulated pathways related to i) immune and inflammatory response, ii) neurotransmitter activity, iii) endothelial and vascular processes and iv) hormonal alterations. The differentially expressed genes are not all direct targets of the vitamin D-VDR pathway and it appears that vitamin D action engages in the crosstalk with estrogen and insulin signaling. The misexpression of the large number of genes observed in this study translates into improved learning and memory performance and a decrease in amyloid plaques and astrogliosis in Tg animals.
Conclusions
This study underlies the multiplicity of action of this potent neurosteroid in an aging and AD-like brain. The classical and non-classical actions of vitamin D3 can act in an additive and possibly synergistic manner to induce neuroprotective activities in a context-specific way.