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Vitamin D and Alzheimer's Disease: Neurocognition to Therapeutics.

Banerjee A, Khemka VK, Ganguly A, Roy D, Ganguly U, Chakrabarti S - Int J Alzheimers Dis (2015)

Bottom Line: The sporadic form of AD accounts for nearly 90% of the patients developing this disease.This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population.Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, ICARE Institute of Medical Sciences and Research, Haldia 721645, India ; Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India.

ABSTRACT
Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients.

No MeSH data available.


Related in: MedlinePlus

Risk factors and pathogenic mechanisms in the aetiopathogenesis of sporadic Alzheimer's disease (AD).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4553343&req=5

fig1: Risk factors and pathogenic mechanisms in the aetiopathogenesis of sporadic Alzheimer's disease (AD).

Mentions: AD is a multifactorial disease and the mechanisms underlying its pathogenesis are complex. Several postmortem evidences, studies in transgenic animal models, and cell-based models (cell lines and primary cortical neurons) have improved our understanding of the pathogenesis of AD [10–14]. These studies have implicated amyloid β (Aβ) accumulation, hyperphosphorylated tau, oxidative stress, metal dysregulation, mitochondrial dysfunction, and inflammatory response as major interconnecting networks leading to neuronal and synaptic degeneration [15–18]. Alterations in the amyloid metabolic cascade constitute an important hypothesis in AD, though none of the theories alone is sufficient to decipher the biochemical and pathological complexities that result in disease progression [19]. Cortical plaques in AD brain primarily contain Aβ protein which is produced from its parent amyloid precursor protein (APP) through sequential hydrolysis by β and γ-secretases [20]. The major species of Aβ are Aβ-40 and Aβ-42 peptides and the latter is predominant in neuritic plaques and has a higher propensity to aggregate and form the characteristic toxic amyloid fibrils in AD [21, 22]. In spite of evidences in support of “amyloid cascade hypothesis” and “tauopathy,” it is still unclear how these events are triggered in the aging brain and how they contribute to the complexity and the heterogeneity of AD. Moreover, it has been established that the etiology of sporadic AD involves multiple gene-environment interactions as well as epigenetic mechanisms (as shown in Figure 1) working in the backdrop of aging brain [23]. An interesting hypothesis in this regard is the Latent Early-life Associated Regulation (LEARn) model which proposes that exposure to various environmental risk factors (heavy metals or nutritional deficiency) in the early developmental life can bring about epigenetic modifications of AD related genes (first hit) which remain latent for many years until a second hit (aging, elevated proinflammatory cytokines, and diet) results in sustained alterations in these genes promoting disease progression [24].


Vitamin D and Alzheimer's Disease: Neurocognition to Therapeutics.

Banerjee A, Khemka VK, Ganguly A, Roy D, Ganguly U, Chakrabarti S - Int J Alzheimers Dis (2015)

Risk factors and pathogenic mechanisms in the aetiopathogenesis of sporadic Alzheimer's disease (AD).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4553343&req=5

fig1: Risk factors and pathogenic mechanisms in the aetiopathogenesis of sporadic Alzheimer's disease (AD).
Mentions: AD is a multifactorial disease and the mechanisms underlying its pathogenesis are complex. Several postmortem evidences, studies in transgenic animal models, and cell-based models (cell lines and primary cortical neurons) have improved our understanding of the pathogenesis of AD [10–14]. These studies have implicated amyloid β (Aβ) accumulation, hyperphosphorylated tau, oxidative stress, metal dysregulation, mitochondrial dysfunction, and inflammatory response as major interconnecting networks leading to neuronal and synaptic degeneration [15–18]. Alterations in the amyloid metabolic cascade constitute an important hypothesis in AD, though none of the theories alone is sufficient to decipher the biochemical and pathological complexities that result in disease progression [19]. Cortical plaques in AD brain primarily contain Aβ protein which is produced from its parent amyloid precursor protein (APP) through sequential hydrolysis by β and γ-secretases [20]. The major species of Aβ are Aβ-40 and Aβ-42 peptides and the latter is predominant in neuritic plaques and has a higher propensity to aggregate and form the characteristic toxic amyloid fibrils in AD [21, 22]. In spite of evidences in support of “amyloid cascade hypothesis” and “tauopathy,” it is still unclear how these events are triggered in the aging brain and how they contribute to the complexity and the heterogeneity of AD. Moreover, it has been established that the etiology of sporadic AD involves multiple gene-environment interactions as well as epigenetic mechanisms (as shown in Figure 1) working in the backdrop of aging brain [23]. An interesting hypothesis in this regard is the Latent Early-life Associated Regulation (LEARn) model which proposes that exposure to various environmental risk factors (heavy metals or nutritional deficiency) in the early developmental life can bring about epigenetic modifications of AD related genes (first hit) which remain latent for many years until a second hit (aging, elevated proinflammatory cytokines, and diet) results in sustained alterations in these genes promoting disease progression [24].

Bottom Line: The sporadic form of AD accounts for nearly 90% of the patients developing this disease.This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population.Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, ICARE Institute of Medical Sciences and Research, Haldia 721645, India ; Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India.

ABSTRACT
Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients.

No MeSH data available.


Related in: MedlinePlus