Role of Vitamin D in Amyloid clearance via LRP-1 upregulation in Alzheimer’s disease: A potential therapeutic target?
Journal of Chemical Neuroanatomy, Volume 85, November 2017, Pages 36-42. https://doi.org/10.1016/j.jchemneu.2017.06.007
- Amyloid clearance majorly contributes to progression of Alzheimer’s Disease.
- LRP-1, located on albuminal side of BBB, is an efflux receptor and substrate to Aβ contributes towards amyloid clearance.
- Vitamin D has been reported to increase expression of LRP-1 and simultaneously amyloid clearance.
Amyloid beta (Aβ) deposition is considered to be one of the primary reason to trigger Alzheimer’s disease (AD). Literature clearly suggests decline in Aβ clearance to be accountable for progression of late onset AD as compared to augmented Aβ production. There may be several pathways for Aβ clearance out of which one of the major pathway is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB) via efflux pumps or receptors. Among Aβ scavenger receptors, low density lipoprotein receptor related protein (LRP-1) has been most extensively studied. LRP-1, is highly expressed in neurons and located on abluminal side of the brain capillaries whose expression decreases in AD patients which give rise to increased cerebral Aβ deposition.
Recent evidences reveal that post 1,25-(OH)2D3 treatment, LRP1 expression increases significantly for both in-vivo and in-vitro studies, since Vitamin D receptors (VDR) are broadly expressed in brain. Biological actions of Vitamin D are mediated via its nuclear hormone receptor vitamin D receptor (VDR) and is found to regulate many genes. Several lines of evidence suggest that VDR deficiency/inhibition can be a potential risk factor for AD and sufficient Vitamin D supplementation is beneficial to prevent AD onset/pathology or slow down the progression of disease. The present review establishes a strong correlation between Vitamin D and LRP-1 and their possible involvement in Aβ clearance and thereby emerging as new therapeutic target.
Alzheimers-Cognition - Overview has the following summary
- FACT: Cognitive decline is 19X more likely if low vitamin D
- FACT: Dementia is associated with low vitamin D levels.
- FACT: Alzheimer’s 21 % more likely if low vitamin D
- FACT: Alzheimer's Disease is 4X less likely if 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: 39 vitamin D and Alz. or Cognition lntervention 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
- 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: By 2024 Omega-3 and high dose Vitamin D will be found to reverse Alzheimer's in humans
- As of 2018 that combination has worked well with Multiple Sclerosis, Sleep, and Cluster Headaches
- All items in category Cognition and vitamin D
- Lower vitamin D in blood causes Alzheimer's Disease (Mendelian gene analysis) – Dec 2019
- Cognitive decline not helped by daily vitamin D getting to just 30 ng – RCT July 2019
- Alzheimer’s is associated with all 7 of the genes which restrict vitamin D from getting to tissues – Sept 2018
- Alzheimer’s (1.2X) and Parkenson’s (1.3X) more likely if poor Vitamin D Receptor – meta-analysis March 2019
- Treating herpes reduced incidence of senile dementia by 10 X (HSV1 reduces VDR by 8X) – 2018
- Body may change gene activation if more Vitamin D is needed by tissue (Schiz. in this case) – Oct 2018
- Alzheimer’s associated with Vitamin D and Vitamin D receptor – video and pdf – Aug 2018
- Cerebral small vessel disease 2.5 X more likely if poor Vitamin D Receptor – Sept 2018
- Alzheimer’s Disease is associated with genes which restrict vitamin D – Aug 2015
- Parkinson's and Alzheimer's: associations with vitamin D receptor genes and race – meta-analysis July 2014
- Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012
- Alzheimer’s patients are genetically 70 percent more likely to be vitamin D in-efficient – Feb 2012
Note above: Alzheimer’s 3 times more likely if poor VDR