What is the role of
Vitamin A in
Alzheimer’s
Disease?
BIOLOGY OF DISEASE LSC-30015
19002410
,Contents
Abstract....................................................................................................................................................... 1
1. Introduction............................................................................................................................................. 2
1.1 Mechanisms and Hallmarks of Alzheimer’s Disease...........................................................................2
1.2 Vitamin A and its Metabolites............................................................................................................ 5
2. Discussion................................................................................................................................................ 8
2.1 Vitamin A and the development of Alzheimer’s.................................................................................8
2.2 VA and the control of gene expression............................................................................................... 9
2.3 How VA can influence neuronal cell differentiation..........................................................................10
2.4 Vitamin A in the Diet........................................................................................................................ 10
2.5 Vitamin A as an Antioxidant............................................................................................................. 11
2.6 Therapeutic potential of VA............................................................................................................. 13
3. Conclusions............................................................................................................................................ 14
Acknowledgements.................................................................................................................................... 14
References................................................................................................................................................. 15
Table of figures:
Figure 1. How tau pathology can cause neuronal cell death via tau aggregation. Under non-pathological
conditions, tau stabilises microtubules of axons necessary for nutrient distribution within the cell.
Otherwise, oxidative stress and the activity of tau kinases cause rapid accumulation of misfolded tau,
which exhibits neurotoxicity within the intracellular space of the neuron and eventual death of the cell
(Saito et al., 2021)........................................................................................................................................ 3
Figure 2 The sources and role of Vitamin A in neural differentiation, oxidative stress and gene regulation
that prevent against AD pathology and the progression of disease. Preformed VA comes from animal
products whereas provitamin A carotenoids are derived from plant products and must be converted to VA
(Rai et al., 2021)........................................................................................................................................... 7
Abstract
There is evidence in literature to suggest a relationship between lower Vitamin A (VA)-
retinol, retinal and retinoic acid (RA)- concentrations and the risk of developing Alzheimer’s
Disease (AD). Hypovitaminosis can be categorised into primary VA deficiency- prolonged
deprivation of VA- and secondary VA deficiency, whereby the vitamin is not stored or
absorbed correctly. As VA is thought to provide a crucial role in the pathogenesis of AD, the
1
, intake of VA in the diet has been found to lessen symptoms of neurodegeneration and slow-
or even reverse- AD as it progresses. So far, existing literature on the role of VA in AD
mainly focuses on its effects in animal models, or fails to address how far VA reduces the
likelihood of neurodegenerative disease compared to other prevailing issues such as genetic
predisposition and the inheritance of risk-associated isoforms. Although AD is commonly
associated with the elderly, the availability of VA in utero has been speculated to impact on
the likelihood of developing AD in later life. Collectively, gene expression, oxidative stress
and buildup of neurotoxic plaque contribute to the neurodegenerative pathway, whereby, the
early use of retinoic acid as a therapeutic strategy could be one way to improve, delay or
prevent symptoms and thus reduce the occurrence and progression of AD.
1. Introduction
1.1 Mechanisms and Hallmarks of Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common type of dementia in adults over 65, accounting
for approximately two-thirds of diagnoses and 7.7 million new cases each year (Brito-
Aguilar, 2019). As a subset of neurodegenerative diseases, AD is a type of tauopathy, defined
by the accumulation of hyperphosphorylated microtubule-associated tau that can spread to
the hippocampus and impact memory formation and retention. This is mainly due to two
cysteine residues within the structure of tau that can form both intramolecular and
intermolecular disulfide bonds with other protein structures in the brain (Walker et al., 2012).
This aggregation causes neurofibrillary tangles to form, which are neurotoxic and lead
directly to the death of neurons (Figure 1).
2
Vitamin A in
Alzheimer’s
Disease?
BIOLOGY OF DISEASE LSC-30015
19002410
,Contents
Abstract....................................................................................................................................................... 1
1. Introduction............................................................................................................................................. 2
1.1 Mechanisms and Hallmarks of Alzheimer’s Disease...........................................................................2
1.2 Vitamin A and its Metabolites............................................................................................................ 5
2. Discussion................................................................................................................................................ 8
2.1 Vitamin A and the development of Alzheimer’s.................................................................................8
2.2 VA and the control of gene expression............................................................................................... 9
2.3 How VA can influence neuronal cell differentiation..........................................................................10
2.4 Vitamin A in the Diet........................................................................................................................ 10
2.5 Vitamin A as an Antioxidant............................................................................................................. 11
2.6 Therapeutic potential of VA............................................................................................................. 13
3. Conclusions............................................................................................................................................ 14
Acknowledgements.................................................................................................................................... 14
References................................................................................................................................................. 15
Table of figures:
Figure 1. How tau pathology can cause neuronal cell death via tau aggregation. Under non-pathological
conditions, tau stabilises microtubules of axons necessary for nutrient distribution within the cell.
Otherwise, oxidative stress and the activity of tau kinases cause rapid accumulation of misfolded tau,
which exhibits neurotoxicity within the intracellular space of the neuron and eventual death of the cell
(Saito et al., 2021)........................................................................................................................................ 3
Figure 2 The sources and role of Vitamin A in neural differentiation, oxidative stress and gene regulation
that prevent against AD pathology and the progression of disease. Preformed VA comes from animal
products whereas provitamin A carotenoids are derived from plant products and must be converted to VA
(Rai et al., 2021)........................................................................................................................................... 7
Abstract
There is evidence in literature to suggest a relationship between lower Vitamin A (VA)-
retinol, retinal and retinoic acid (RA)- concentrations and the risk of developing Alzheimer’s
Disease (AD). Hypovitaminosis can be categorised into primary VA deficiency- prolonged
deprivation of VA- and secondary VA deficiency, whereby the vitamin is not stored or
absorbed correctly. As VA is thought to provide a crucial role in the pathogenesis of AD, the
1
, intake of VA in the diet has been found to lessen symptoms of neurodegeneration and slow-
or even reverse- AD as it progresses. So far, existing literature on the role of VA in AD
mainly focuses on its effects in animal models, or fails to address how far VA reduces the
likelihood of neurodegenerative disease compared to other prevailing issues such as genetic
predisposition and the inheritance of risk-associated isoforms. Although AD is commonly
associated with the elderly, the availability of VA in utero has been speculated to impact on
the likelihood of developing AD in later life. Collectively, gene expression, oxidative stress
and buildup of neurotoxic plaque contribute to the neurodegenerative pathway, whereby, the
early use of retinoic acid as a therapeutic strategy could be one way to improve, delay or
prevent symptoms and thus reduce the occurrence and progression of AD.
1. Introduction
1.1 Mechanisms and Hallmarks of Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common type of dementia in adults over 65, accounting
for approximately two-thirds of diagnoses and 7.7 million new cases each year (Brito-
Aguilar, 2019). As a subset of neurodegenerative diseases, AD is a type of tauopathy, defined
by the accumulation of hyperphosphorylated microtubule-associated tau that can spread to
the hippocampus and impact memory formation and retention. This is mainly due to two
cysteine residues within the structure of tau that can form both intramolecular and
intermolecular disulfide bonds with other protein structures in the brain (Walker et al., 2012).
This aggregation causes neurofibrillary tangles to form, which are neurotoxic and lead
directly to the death of neurons (Figure 1).
2
