Alzheimer's disease in Vitamin A Points of view

 Kyle J. Norton(Draft Article)

Alzheimer's disease is a brain disorder correlated with major reductions of neurons to the respective target areas through destruction of brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal.
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease.

Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity, causing dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
1. Retinols
Retinoids, derived from Vitamin A involve in cellular regulatory processes including cell differentiation, neurite outgrowth and defense against oxidative stress. In patients with Alzheimers; disease, plasma levels including retinols was found to be sgnificantly lower of that may suggested the vascular comorbidities of patients with AD may be result of certain degrees of depletion of the antioxidant defense system(1). The study of Kanazawa University Graduate School of Medical Science, indicated that vitamin A (retinol, retinal and retinoic acid) inhibited the formation, extension and destabilizing effects of β-amyloid fibrils and  the oligomerization of Aβ (Aβ40 and Aβ42)(2) and Aβ1-16 and Aβ25-35(3). According to University Hospitals Case Medical Center, Retinoids may influence Amyloid beta processing upregulation of alpha secretase via ADAM10 and inhibit formation of Amyloid fibrils(4) with these properties of retinoids are relevant to theories of Alzheimer's disease pathogenesis.
Retinoic acid receptor (RAR) α systemactivated by both all-trans retinoic acid and 9-cis retinoic acid sginalling is found downreguated by amyloid beta (Aβ) in Alzheimers patients. There fore stimulation of the RARα signalling pathway using a synthetic agonist may be effective reverse the the cognitive impairment caused by amyloid beta (Aβ)(5). In Streptozotocin (STZ) induced mice, all-trans-retinoic acid (ATRA) treatment significantly attenuated STZ-induced memory deficits, biochemical and histopathological alterations(6).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin)
Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects.
The study of Plasma Levels of HDL and Carotenoids in Alzheimer's patients indicated the protective effects of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia(7). The study of Rayalaseema University, Kurnool, Andhra Pradesh showed the anti oxidant effects of carotenoids in reduced symptoms of Alzheimer's diseases through inhibition of amyloid beta (Aβ) formation, deposition and fibril(8). Plasma of carotenoids may be used as a marker to determine the severity of AD. According to Oregon Health and Science University, there was an association between higher carotenoids levels and DHA and higher MMSE (tests that screen for Alzheimer's,)scores, supports a protective role of both types of nutrients in AD(9)(10). In a in the community-dwelling elderly study indicated that use of supplemental antioxidants (vitamins A, C, or E, plus selenium or zinc) is associated with reduction of cognitive decline(11) with vitamin A is found to be destabilization of beta-amyloid fibrils (fAbeta)(12).

Taking altogether, plasma levels of vitamin A may be an indication of marker in identification of the early onset of Alzheimer's disease which may be beneficiary with the intake of vitamin A, regardless to its forms. Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

References
(1) [Influence of vascular comorbidities on the antioxidant defense system in Alzheimer's disease].

[Article in German by Polidori MC¹, Stahl W, De Spirt S, Pientka L(PubMed)

(2) Vitamin A and Alzheimer's disease by Ono K¹, Yamada M.(PubMed)
(3) Vitamin A has anti-oligomerization effects on amyloid-β in vitro by Takasaki J¹, Ono K, Yoshiike Y, Hirohata M, Ikeda T, Morinaga A, Takashima A, Yamada M(PubMed)

(4) Retinoids for treatment of Alzheimer's disease by Lerner AJ¹, Gustaw-Rothenberg K, Smyth S, Casadesus G(PubMed)
(5) Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist by Goncalves MB¹, Clarke E, Hobbs C, Malmqvist T, Deacon R, Jack J, Corcoran JP(PubMed)
(6) All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type by Sodhi RK¹, Singh N.(PubMed)
(7) Plasma Levels of HDL and Carotenoids are Lower in Dementia Patients with Vascular Comorbidities by Dias IH¹, Polidori MC², Li L¹, Weber D³, Stahl W⁴, Nelles G⁵, Grune T³, Griffiths HR¹.(PubMed)
(8) Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models by Obulesu M¹, Dowlathabad MR, Bramhachari PV.(PubMed)
(9) Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity by Wang W¹, Shinto L, Connor WE, Quinn JF.(PubMed)
(10) Plasma levels of antioxidants are not associated with Alzheimer's disease or cognitive decline by Engelhart MJ¹, Ruitenberg A, Meijer J, Kiliaan A, van Swieten JC, Hofman A, Witteman JC, Breteler MM.(PubMed)
(11) Is antioxidant use protective of cognitive function in the community-dwelling elderly? by Gray SL¹, Hanlon JT, Landerman LR, Artz M, Schmader KE, Fillenbaum GG.(PubMed)
(12) Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro by Ono K¹, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M.(PubMed)