Nutrients required for phospholipid synthesis are lower in blood and cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease dementia

Wijk, Nick van; Slot, Rosalinde E.R.; Duits, Flora H.; Strik, Marieke; Biesheuvel, Egbert; Sijben, John; Blankenstein, Marinus A.; Bierau, Jörgen; Flier, Wiesje M. van der; Scheltens, Philip; Teunissen, Charlotte E.

doi:10.1016/j.dadm.2017.04.005

Cited by 20 publications

(18 citation statements)

References 52 publications

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“…Methionine loading increases brain homocysteine, Aβ and phospho-tau in mouse models [ 58 ]. Decreased expression in AD CP of the methionine-degrading gene may relate to elevated homocysteine levels in CSF [ 59 ]. The impact of augmented CSF homocysteine on raising brain Aβ and tau hints that additional methionine gene studies on CP transcription factors and metabolism in neurodegenerative diseases are needed.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

Stopa

Tanis

Miller

et al. 2018

Fluids Barriers CNS

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BackgroundIn Alzheimer’s disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood–cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.MethodsTranscriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP. RNA from post-mortem samples of the entire lateral ventricular choroid plexus was extracted from 6 healthy controls (Ctrl), 7 patients with advanced (Braak and Braak stage III–VI) Alzheimer’s disease (AD), 4 with frontotemporal dementia (FTD) and 3 with Huntington’s disease (HuD). Statistics and agglomerative clustering were accomplished with MathWorks, MatLab; and gene set annotations by comparing input sets to GeneGo (http://www.genego.com) and Ingenuity (http://www.ingenuity.com) pathway sets. Bonferroni-corrected hypergeometric p-values of < 0.1 were considered a significant overlap between sets.ResultsPronounced differences in gene expression occurred in CP of advanced AD patients vs. Ctrls. Metabolic and immune-related pathways including acute phase response, cytokine, cell adhesion, interferons, and JAK-STAT as well as mTOR were significantly enriched among the genes upregulated. Methionine degradation, claudin-5 and protein translation genes were downregulated. Many gene expression changes in AD patients were observed in FTD and HuD (e.g., claudin-5, tight junction downregulation), but there were significant differences between the disease groups. In AD and HuD (but not FTD), several neuroimmune-modulating interferons were significantly enriched (e.g., in AD: IFI-TM1, IFN-AR1, IFN-AR2, and IFN-GR2). AD-associated expression changes, but not those in HuD and FTD, were enriched for upregulation of VEGF signaling and immune response proteins, e.g., interleukins. HuD and FTD patients distinctively displayed upregulated cadherin-mediated adhesion.ConclusionsOur transcript data for human CP tissue provides genomic and mechanistic insight for differential expression in AD vs. FTD vs. HuD for stromal as well as epithelial components. These choroidal transcriptome characterizations elucidate immune activation, tissue functional resiliency, and CSF metabolic homeostasis. The BCSFB undergoes harmful, but also important functional and adaptive changes in neurodegenerative diseases; accordingly, the enriched JAK-STAT and mTOR pathways, respectively, likely help the CP in adaptive transcription and epithelial repair and/or replacement when harmed by neurodegeneration pathophysiology. We anticipate that these precise CP translational data will facilitate pharmacologic/transgenic therapies to alleviate dementia.Electronic supplementary materialThe online version of this article (10.1186/s12987-018-0102-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

Stopa

Tanis

Miller

et al. 2018

Fluids Barriers CNS

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“…By improving phospholipid metabolism, lifestyle interventions may help to preserve neuronal functions and maintain cognitive performance. Evidence suggests that key nutrients required for phospholipid synthesis are lower in the blood and cerebrospinal fluid of patients with MCI [84] and such nutritional deficiencies may impair the brain’s ability to maintain neuronal functions.…”

Section: Rationale For Nutritional Interventionsmentioning

confidence: 99%

Souvenaid in the management of mild cognitive impairment: an expert consensus opinion

et al. 2019

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Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. Methods An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Summary of opinion Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer’s disease (AD), including those with MCI due to AD (prodromal AD). Conclusion Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a multimodal management approach including lifestyle risk factor modification and consideration of the multinutrient Souvenaid. Electronic supplementary material The online version of this article (10.1186/s13195-019-0528-6) contains supplementary material, which is available to authorized users.

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“…It is plausible that HDL‐related PLs and FC constitute a buffer participating to the repair of the injured cells membranes since lack of nutrients required for PL synthesis is observed in patients with CI compared to normal subjects . Lipid rafts are microdomains of neurons and astrocytes membranes, with accumulation of HDL‐related FCs, specific proteins, sphingomyelins, and free fatty acids.…”

Section: Role Of Hdls In Neurological Diseasesmentioning

confidence: 99%

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

et al. 2019

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Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid‐related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high‐density lipoproteins (HDLs) and their major protein component, apoA‐I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL‐related neurological disorders.

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Nutrients required for phospholipid synthesis are lower in blood and cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease dementia

Cited by 20 publications

References 52 publications

Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

Souvenaid in the management of mild cognitive impairment: an expert consensus opinion

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

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