Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer’s disease patients

Abstract

Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer's disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1β or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients.

Serum vitamin D in patients with mild cognitive impairment and Alzheimer's disease

“…However, serum 25(OH)D3 is negatively correlated with TNFα, IL-1β or IL-6 levels in healthy subjects and patients with MCI, but positively with late-onset AD (Dursun et al, 2016). As TNF is increased in AD (Gezen-Ak et al, 2013), it is possible that the increased TNFα is responsible for the decreased 25(OH)D 3 .…”

“…It has been reported that 1,25(OH) 2 D 3 is increased by parathyroid hormone (Eastell et al., ) and cytokines, including TNF (Bikle & Vitamin, ). However, serum 25(OH)D3 is negatively correlated with TNFα, IL‐1β or IL‐6 levels in healthy subjects and patients with MCI, but positively with late‐onset AD (Dursun et al., ). As TNF is increased in AD (Gezen‐Ak et al., ), it is possible that the increased TNFα is responsible for the decreased 25(OH)D 3 .…”

“…There is a reciprocal relationship between vitamin D and AD. It has been reported that 25(OH)D 3 is reduced in late-onset AD, and vitamin D deficiency is regarded as a risk factor for ApoEε4 noncarrier patients with AD (Dursun et al, 2016). On the other hand, supplementation with vitamin D derivatives decreases the risk of AD (Dean, Bellgrove, & Hall, 2011).…”

Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin

“…Eyles et.al have meticulously reviewed the evidence that vitamin D differentiates brain cells, regulates axonal growth and calcium signaling directly in the brain, modulates the production of brain-derived reactive oxygen species and stimulates the production of neurotrophic factors which are relevant to the variety of neuropsychiatric conditions and also neurodegenerative disorders [ 1 ]. Our in vivo and in vitro studies [ 2 – 8 ] and other publications in the field support the effect of vitamin D on neurodegeneration and Alzheimer’s disease (AD), but the cellular mechanisms involved in this effect is still unknown. The intriguingly complex effects of vitamin D receptor (VDR) silencing or 1,25-Dihydroxyvitamin D 3 treatments on α-, β-, γ-secretases, APP and the obvious result on amyloid production that we demonstrated in our previous study [ 9 ] indicated that some of the vitamin D/its receptors depended regulations might not be explained solely by transcriptional regulation.…”

Advances in clinical neurology through the journal “Neurological Sciences” (2015–2016)

“…Vitamin D deficiency presents a greater risk for ApoEe4 non-carrier AD patients than for e4 carriers [107]. Nmethyl-D-aspartate receptors (NMDARs) play a pivotal role in the synaptic transmission and synaptic plasticity thought to underlie learning and memory and have been recently implicated in Alzheimer's disease [108].…”