NUGENIS – Touchpoint Epigenetics

Recent Findings of Research

RESEARCH

NUGENIS wants to promote research into applied epigenetics. We are open to share our knowledge and promote exchange on a professional level. We are happy to support young scientists deciding on their research topic with ideas and contacts to research groups.

We are looking forward to your scientific questions under office@nugenis.eu

DNA Methylation - NUGENIS supports the DNA Methylation with Applied Epigenetics

SCIENTIFIC BACKGROUND

Further recommended reading on this topic

(August 2016)

Bottiglieri T, Reynolds EH, Toone BK, Carney MW. CSF S-adenosylmethionine in neuropsychiatric disorders. Lancet 1991 Jul 13;338(8759):121

Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB. A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. J Nutr Health Aging 2010 Mar;14(3):224-30

Chouliaras L, Rutten BP, Kenis G, Peerbooms O, Visser PJ, Verhey F, et al. Epigenetic regulation in the pathophysiology of Alzheimer’s disease. Prog Neurobiol 2010 Apr;90(4):498-510

de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 2011 Jul 21

Fontanari D, Di Palma C, Giorgetti G, Violante F, Voltolina M. Effects of S-adenosyl-L-methionine on cognitive and vigilance functions in the elderly. Current Therapeutic Research 55 [6], 682-689. 1994

Fuso A, Nicolia V, Ricceri L, Cavallaro RA, Isopi E, Mangia F, et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging 2012 Jan 4.

Fuso A, Scarpa S. One-carbon metabolism and Alzheimer’s disease: is it all a methylation matter? Neurobiol Aging 2011 Jul;32(7):1192-5

Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005 Jan;28(1):195-204

Goren JL, Stoll AL, Damico KE, Sarmiento IA, Cohen BM. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy 2004 Nov;24(11):1501-7

Levkovitz Y, Alpert JE, Brintz CE, Mischoulon D, Papakostas GI. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. J Affect Disord 2012 Feb;136(3):1174-8

Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic changes in Alzheimer’s disease: decrements in DNA methylation. Neurobiol Aging 2010 Dec;31(12):2025-37

Refsum H, Smith AD. Low vitamin B-12 status in confirmed Alzheimer’s disease as revealed by serum holotranscobalamin. J Neurol Neurosurg Psychiatry 2003 Jul;74(7):959-61

Remington R, Lortie JJ, Hoffmann H, Page R, Morrell C, Shea TB. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension. J Alzheimers Dis. 2015 Oct 1;48(3):591-5

Remington R, Chan A, Paskavitz J, Shea TB. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen 2009 Feb;24(1):27-33

Thompson MA, Bauer BA, Loehrer LL, Cha SS, Mandrekar JN, Sood A, et al. Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial. J Altern Complement Med 2009 May;15(5):523-9

Wang SC, Oelze B, Schumacher A. Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One 2008;3(7):e2698

Zellner M, Baureder M, Rappold E, Bugert P, Kotzailias N, Babeluk R, et al. Comparative platelet proteome analysis reveals an increase of monoamine oxidase-B protein expression in Alzheimer’s disease but not in non-demented Parkinson’s disease patients. J Proteomics 2012 Jan 17.

Zellner M, Babeluk R, Jakobsen LH, Gerner C, Umlauf E, Volf I, et al. A proteomics study reveals a predominant change in MaoB expression in platelets of healthy volunteers after high protein meat diet: relationship to the methylation cycle. J Neural Transm 2011 May;118(5):653-62

Monoamine oxidase B concentration increased to a pathological level has also been seen in these patients:

Smokers

Launay J-M, Del Pino M, Chironi G, et al. Smoking Induces Long-Lasting Effects through a Monoamine-Oxidase Epigenetic Regulation. Tailleux L, ed. PLoS ONE. 2009;4(11):e7959 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775922]

People on long-term medication with proton pump inhibitors (PPI) to block stomach acid

Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, Brettschneider C, König HH, Werle J, Weyerer S, Luppa M, Riedel-Heller SG, Fuchs A, Pentzek M, Weeg D, Bickel H, Broich K, Jessen F, Maier W, Scherer M. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015 Aug;265(5):419-28 [http://www.ncbi.nlm.nih.gov/pubmed/25341874]

Possible pathomechanisms of homocysteine in the brain – hyperphosphorylated tau protein

Hara J, Shankle WR, Barrentine LW, Curole MV. Novel Therapy of Homocysteinemia in Mild Cognitive Impairment, Alzheimer’s Disease, and Other Dementing Disorders. J Nutrition Health Aging 2016; 20(8): 825-834 [http://www.ncbi.nlm.nih.gov/pubmed/27709231] 

Linnebank M, Popp J, Smulders Y, Smith D, Semmler A, Farkas M, Kulic L, Cvetanovska G, Blom H, Stoffel-Wagner B, Kölsch H, Weller M, Jessen F. S-adenosylmethionine is decreased in the cerebrospinal fluid of patients with Alzheimer’s disease. Neurodegener Dis 2010;7(6):373-8 [http://www.ncbi.nlm.nih.gov/pubmed/20523031]

Popp J, Lewczuk P, Linnebank M, Cvetanovska G, Smulders Y, Kölsch H, Frommann I, Kornhuber J, Maier W, Jessen F. Homocysteine metabolism and cerebrospinal fluid markers for Alzheimer’s disease. J Alzheimers Dis 2009;18(4):819-28 [http://www.ncbi.nlm.nih.gov/pubmed/19661622]

Siuda J, Gorzkowska A, Patalong-Ogiewa M, Kryzystanek E, Czech E, Wiechula B, Garczorz W, Danch A, Jasinska-Myga B, Opala G. From mild cognitive impairment to Alzheimer’s disease – influence of homocysteine, vitamin B12 and folate on cognition over time: results from one-year follow-up. Neurol Neurochir Pol 2009, Jul-Aug; 43(4):321-329 [http://www.ncbi.nlm.nhi.gov/pubmed/19742390]

Smith DE, Smulders YM, Blom HJ, Popp J, Jessen F, Semmler A, Farkas M, Linnebank M. Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid. Clin Chem Lab Med 2012, 50(9):1641-7 [http://www.ncbi.nlm.nih.gov/pubmed/22962226]

Sontag E, Nunbhakdi-Craig V, Sontag JM, Diaz-Arrastia R, Ogris E, Dayal S, Lentz SR, Arning E, Bottiglieri T Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci 2007, 27(11).2751-9 [http://www.ncbi.nlm.nih.gov/pubmed/17360897]

Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL 3rd . Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 2004, 63(10).1080-91 [http://www.ncbi.nlm.nih.gov/pubmed/15535135]

Think about your brain:

Huriye ErcanChristina Maria ReumillerJacqueline MühlbergerFelicia HsuGeorg Johannes SchmidtEllen UmlaufIngrid MillerEduard RappoldJohannes AttemsRudolf OehlerMaria Zellner. Platelets mirror changes in the frontal lobe antioxidant system in Alzheimer’s disease. Alzheimer’s & Dementia: Volume 21, Issue 4. First published: 06 April 2025. https://doi.org/10.1002/alz.7011

Mild brain injury

Yang, Shun-Tai et al. Accumulation of amyloid in cognitive impairment after mild traumatic brain injury. Journal of the Neurological Sciences , Volume 349, Issue 1, 99-104 [http://www.ncbi.nlm.nih.gov/pubmed/25586534]

Ingestion of aluminium

Singla N, Dhawan D.K. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration. Mol Neurobiol (2016) [http://www.ncbi.nlm.nih.gov/pubmed/26742519]

Ademetionine and its effects on sleep

Arnold, O. et al. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. European Neuropsychopharmacology , Volume 15, Issue 5, 533-543 [http://www.ncbi.nlm.nih.gov/pubmed/16046102]

News from the 8th Clinical Trials on Alzheimer’s Disease (CTAD) Congress in Barcelona, Spain (2015)

Healthy lifestyle substantially reduce risks for cognitive decline during aging

A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.

Miia Kivipelto, Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland Karolinska Institute Center for Alzheimer Research, Stockholm, Sweden

Aerobic Exercise reverse aging effects of the brain; 45-60 minutes, four times per week, after six months significant effects

Laura Baker, Ph.D., principal investigator of the study and a cognitive neuroscientist at Wake Forest Baptist Medical Center

Drug developments

Mao-B inhibitor sembragiline from Roche did not improve cognitive functions of AD patients but improves neuropsychiatric scores.

Rachelle S Doody Alzheimer’s Disease and Memory Disorders Center, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA