Volume 6, Issue 1, January 2017, Page: 1-19
Alzheimer’s Disease – The Past, the Present and the Future
Benson Opare Asamoah Botchway, Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
Ishwari Chandran Iyer, Faculty of Basic Medicine, Zhejiang University School of Medicine, Hangzhou, China
Received: Dec. 20, 2016;       Accepted: Jan. 7, 2017;       Published: Feb. 3, 2017
DOI: 10.11648/j.sjcm.20170601.11      View  8883      Downloads  257
Alzheimer’s disease (hereafter: AD) is an irreversible, slowly progressive disease of the brain, most often categorized under the umbrella term ‘neurodegeneration’. It is said to be a progressive disease in a sense that the symptoms associated with AD, the most common one being difficulty in remembering recent events, kick in steadily with the symptoms getting worse as time goes on, leading to the demise of affected person as they eventually lose their bodily functions. Other symptoms associated with AD include language problems, mood swings and disorientation. This report seeks to address the history, current as well as the future state of AD by taking into consideration the probable causes and preventive mechanisms together with the treatment methods.
Alzheimer’s Disease, Neurodegeneration, Causes, Preventive Mechanism, Treatment Methods, Mood Swings, Disorientation
To cite this article
Benson Opare Asamoah Botchway, Ishwari Chandran Iyer, Alzheimer’s Disease – The Past, the Present and the Future, Science Journal of Clinical Medicine. Vol. 6, No. 1, 2017, pp. 1-19. doi: 10.11648/j.sjcm.20170601.11
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lock, M. M. (2013). The Alzheimer conundrum: Entanglements of dementia and aging. United States: Princeton University Press.
n/a. (2011, April 18). AlzGene. Retrieved December 9, 2016, from Alzforum, http://www.alzgene.org/TopResults.asp
Vorvick, L. J. (2014, February 11). Swelling. Retrieved May 7, 2016, from U. S. National Library of Medicine: Medline Plus, https://www.nlm.nih.gov/medlineplus/ency/article/003103.htm.
DeMarco, B. (2015, December 10). What’s the difference between Alzheimer’s and dementia Retrieved from http://www.alzheimersreadingroom.com/2014/08/difference-between-alzheimers-and-dementia.html.
The Fisher Center. (2016). Dementia vs. Alzheimer’s. Retrieved April 26, 2016, from The Fisher Center for Alzheimer’s Research Foundation, https://www.alzinfo.org/understand-alzheimers/dementia/.
About Alzheimer’s disease: Alzheimer’s basics. (2014, May 22). Retrieved April 29, 2016, from National Institute on Aging, https://www.nia.nih.gov/alzheimers/topics/alzheimers-basics.
Corso, J. A. (Ed.). (2011). Perspectives on Alzheimer’s disease. United States: Nova Science Publishers.
Steele, J. Alzheimer disease history: How did AD come to be? Retrieved April 30, 2016, from Glutathione Disease Cure, http://www.glutathionediseasecure.com/alzheimer-disease-history.html.
Berrios, G., E. (2014, October 14). The history of Alzheimer’s disease. Retrieved April 26, 2016, from Wellcome Collection, http://wellcomecollection.org/history-alzheimers-disease.
Turnera, P. R., O’Connorb, K., Tatea, W. P., & Abrahamb, W. C. (2003). Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Progress in Neurobiology, 70 (1), 1–32. Doi:10.1016/S0301-0082 (03) 00089-3.
Association, A. (2016a). Alzheimer’s & brain research milestones | research center | Alzheimer’s association. Retrieved April 26, 2016, from Alzheimer’s Association, http://www.alz.org/research/science/major_milestones_in_alzheimers.asp#progress.
Contestabile, A. (2011). The history of the cholinergic hypothesis. Behavioural Brain Research, 221 (2), 334–340. Doi:10.1016/j.bbr.2009.12.044.
Hammel, P., Larrey, D., Bernuau, J., Kalafat, M., Fréneaux, E., Babany, G., … Benhamou, J.-P. (1990). Acute hepatitis after Tetrahydroaminoacridine administration for Alzheimerʼs disease. Journal of Clinical Gastroenterology, 12 (3), 329–331. Doi:10.1097/00004836-199006000-00021.
LLC, W. (2012, August 9). Cognex (tacrine) dosing, indications, interactions, adverse effects, and more. Retrieved April 26, 2016, from Medscape, http://reference.medscape.com/drug/tacrine-343070.
Tacrine. (2016, March 24). Retrieved April 26, 2016, from Livertox, http://www.livertox.nih.gov/Tacrine.htm.
Shin, R., Iwaki, T., Kitamoto, T., & Tateishi, J. (1991). Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer’s disease brain tissues. Laboratory investigation; a journal of technical methods and pathology., 64 (5), 693–702. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1903170.
Reference, G. H. (2016a, April 20). MAPT. Retrieved April 26, 2016, from Genetics Home Reference, https://ghr.nlm.nih.gov/gene/MAPT#sourcesforpage.
Alzheimer’s Association. Alzheimer’s changes the brain - Alzheimer’s association. Retrieved May 1, 2016b, from Alzheimer’s Association, https://www.alz.org/braintour/alzheimers_changes.asp.
Reference, G. H. (2016c, April 20). Chromosome 21. Retrieved April 26, 2016, from Genetics Home Reference, https://ghr.nlm.nih.gov/chromosome/21#glossary.
Taniguchi, T., Kawamata, T., Mukai, H., Hasegawa, H., Isagawa, T., Yasuda, M., … Tanaka, C. (2000). Phosphorylation of Tau is regulated by PKN. Journal of Biological Chemistry, 276 (13), 10025–10031. Doi:10.1074/jbc.m007427200.
Van Dyke, K. (1997). The possible role of peroxynitrite in Alzheimer’s disease: A simple hypothesis that could be tested more thoroughly. Medical Hypotheses, 48 (5), 375–380. Doi:10.1016/s0306-9877 (97) 90031-1.
Leonard, W. Alzheimer’s disease prevention. Retrieved May 1, 2016, from Heathline, http://www.healthline.com/health/alzheimers-disease-prevention.
Brion, J. (1998). Neurofibrillary tangles and Alzheimer’s disease. European neurology., 40 (3), 130–40. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9748670.
Prince, M., Guerchet, M., & Prina, M. (2015). The Epidemiology And Impact of Dementia Current State and Future Trends. Retrieved from http://www.who.int/mental_health/neurology/dementia/dementia_thematicbrief_epidemiology.pdf?ua=1.
Brain changes in Alzheimer’s disease. (2013). Retrieved April 30, 2016, from Dementia Care Central, http://www.dementiacarecentral.com/aboutdementia/alzheimers/changes/.
Nazir, T. (2011). Lecture on Alzheimer’s disease. Neuropharmacology module, BSc. Pharmaceutical Science, MS3013N. London Metropolitan University. 22 February 2011.
Diamond, J. (2011, October). Alzheimer’s disease: What’s it all about? Where do we stand in the search for a cure? Retrieved from http://brainxchange.ca/Public/Files/Events/National/ADandCurrentResearch_DrJackDiamond.aspx
Newsholme, P., Procopio, J., Lima, M. M. R., Pithon-Curi, T. C., & Curi, R. (2003). Glutamine and glutamate? Their central role in cell metabolism and function. Cell Biochemistry and Function, 21 (1), 1–9. Doi:10.1002/cbf.1003
Solfrizzi, V., Panza, F., Frisardi, V., Seripa, D., Logroscino, G., Imbimbo, B. P., & Pilotto, A. (2011). Diet and Alzheimer’s disease risk factors or prevention: The current evidence. Expert Review of Neurotherapeutics, 11 (5), 677–708. Doi:10.1586/ern.11.56.
McCaddon, A. (2006). Nutrition journal. Nutrition Journal, 5 (6),. Doi:10.1186/1475-2891-5-6
Association, A. (2016b). Current treatments, Alzheimer’s & dementia | research center | Alzheimer’s association. Retrieved April 26, 2016, from Alzheimer’s Association, http://www.alz.org/research/science/alzheimers_disease_treatments.asp#approved
Reference, G. H. (2016b, April 20). APP. Retrieved April 26, 2016, from Genetics Home Reference, https://ghr.nlm.nih.gov/gene/APP#synonyms.
Reference, G. H. (2016d, April 20). Alzheimer disease. Retrieved April 26, 2016, from Genetics Home Reference, https://ghr.nlm.nih.gov/condition/alzheimer-disease#genes.
Association, A. (2016c). Alzheimer’s drug treatment horizon | research center | Alzheimer’s association. Retrieved April 27, 2016, from Alzheimer’s Association, http://www.alz.org/research/science/alzheimers_treatment_horizon.asp.
Staff, M. C. (2016). Alzheimer’s treatments: What’s on the horizon? Alzheimer’s treatments: What’s on the horizon? Mayoclinic. Retrieved from http://www.mayoclinic.org/alzheimers-treatments/art-20047780.
Chen, J., Li, S., Sun, W., & Li, J. (2015). Anti-diabetes drug Pioglitazone Ameliorates Synaptic defects in AD transgenic mice by inhibiting Cyclin-Dependent Kinase5 activity. PLOS ONE, 10 (4), e0123864. Doi:10.1371/journal.pone.0123864.
Cerespir. CSP-1103 overview. Retrieved April 27, 2016, from Cerespir, http://www.cerespir.com/csp-1103-overview/.
Lee, G., Thangavel, R., Sharma, V. M., Litersky, J. M., Bhaskar, K., Fang, S. M., … Ksiezak-Reding, H. (2004). Phosphorylation of Tau by Fyn: Implications for Alzheimer’s disease. Journal of Neuroscience, 24 (9), 2304–2312. Doi:10.1523/jneurosci.4162-03.2004.
Chin, J., Palop, J. J., Puoliväli, J., Mucke, L., Massaro, C., Bien-Ly, N., … Masliah, E. (2005). Fyn Kinase induces Synaptic and cognitive Impairments in a transgenic mouse model of Alzheimer’s disease. Journal of Neuroscience, 25 (42), 9694–9703. Doi:10.1523/jneurosci.2980-05.2005.
Nygaard, H. B., Wagner, A. F., Bowen, G. S., Good, S. P., MacAvoy, M. G., Strittmatter, K. A., … Van Dyck, C. H. (2015). A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer’s disease. Alzheimer’s Research & Therapy, 7 (1), 35. doi:10.1186/s13195-015-0119-0.
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., … Mohs, R. (2014). Phase 3 trials of Solanezumab for mild-to-moderate Alzheimer’s disease. New England Journal of Medicine, 370 (4), 311–321. Doi:10.1056/nejmoa1312889.
BioPharma, P. Solanezumab. Retrieved April 27, 2016, from PDL BioPharma, http://pdl.com/technology-products/product-pipeline/solanezumab/.
Neurimmune. (2015, March 20). Biogen IDEC Presents Positive Interim Results From Phase 1B study at 2015 AD/PD Conference: Aducanumab (BIIB037) Reduced Brain Amyloid Plaque Levels and Slowed Cognitive Decline in Patients with Prodromal or Mild Alzheimer’s disease. Retrieved April 27, 2016, from Neurimmune, http://www.neurimmune.com/newsartikel/20032015-biogen-idec-presents-positive-interim-results-from-phase-1b-study-at-adpd-conference.html.
Jeffrey, S. (2015, May 11). More Positive Data on Aducanumab in Alzheimer’s. Retrieved April 27, 2016, from Medscape, http://www.medscape.com/viewarticle/844502.
Thompson, Jr, D. (2016). What’s ahead in the Alzheimer’s research pipeline? Retrieved April 27, 2016, from Everyday Health, http://www.everydayhealth.com/alzheimers/alzheimers-research-and-future-treatments.aspx.
Reference, G. H. (2016e, April 20). PSEN1. Retrieved April 26, 2016, from Gene, https://ghr.nlm.nih.gov/gene/PSEN1#synonyms.
Reference, G. H. (2016f, April 20). PSEN2. Retrieved April 26, 2016, from G, https://ghr.nlm.nih.gov/gene/PSEN2.
Reference, G. H. (2016g, April 20). APOE. Retrieved April 26, 2016, from G, https://ghr.nlm.nih.gov/gene/APOE.
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006). Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proceedings of the National Academy of Sciences, 103 (15), 5644–5651. Doi:10.1073/pnas.0600549103.
Tuszynski, M. H., et al. (2015). Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease. JAMA Neurology, published online August 24, 2015. DOI: 10.1001/jamaneurol.2015.1807.
Parra-Damas A., Valero J., Chen M., España J., Martin E., Ferrer I., Rodríguez-Alvarez J. and Saura C.A. Crtc1 Activates a Transcriptional Program Deregulated at Early Alzheimer's Disease-Related Stages. Journal of Neuroscience, April 2014 DOI: 10.1523/JNEUROSCI.5288-13.2014.
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999). The cholinergic hypothesis of Alzheimer’s disease: A review of progress. Journal of Neurology, Neurosurgery & Psychiatry, 66 (2), 137–147. Doi:10.1136/jnnp.66.2.137.
Town, T., Nikolic, V., & Tan, J. (2005). The microglial “activation” continuum: from innate to adaptive responses. Journal of Neuroinflammation, 2 (1), 24. Doi:10.1186/1742-2094-2-24.
Gandy, S., Haroutunian, V., DeKosky, S. T., Sano, M., & Schadt, E. E. (2013). CR1 and the “Vanishing Amyloid” hypothesis of Alzheimer’s disease. Biological Psychiatry, 73 (5), 393–395. Doi:10.1016/j.biopsych.2013.01.013.
Kaufman, A. C., Salazar, S. V., Haas, L. T., Yang, J., Kostylev, M. A., Jeng, A. T., … Strittmatter, S. M. (2015). Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Annals of Neurology, 77 (6), 953–971. Doi:10.1002/ana.24394.
Weitz, T. M., & Town, T. (2012). Microglia in Alzheimer’s disease: It’s all about context. International Journal of Alzheimer’s Disease, 2012 (2012), 1–11. doi:10.1155/2012/314185.
Reger, B. (2002, August). Alzheimer’s disease: A brief history and avenues for current research. Retrieved April 29, 2016, from Jour, http://legacy.jyi.org/volumes/volume6/issue2/features/reger.html.
Avila, J., Lucas, J., Perez, M., & Hernandez, F. (2004). Role of Tau protein in both physiological and pathological conditions. Physiological Reviews, 84 (2), 361–384. Doi:10.1152/physrev.00024.2003.
Mandal, A. (2014, October 20). What are Tau proteins? Retrieved April 30, 2016, from Life Sciences, http://www.news-medical.net/life-sciences/What-are-Tau-Proteins.aspx .
Mohandas, E., Rajmohan, V., & Raghunath, B. (2009). Neurobiology of Alzheimer′s disease. Indian Journal of Psychiatry, 51 (1), 55–61. Doi:10.4103/0019-5545.44908.
Alzheimer’s disease fact sheet. (2015, May). Retrieved May 1, 2016, from National Institute on Aging, https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet.
Association, A. Inside the Brain: Alzheimer’s Brain Tour. Retrieved May 1, 2016, from Alzheimer’s Association, http://www.alz.org/research/science/alzheimers_brain_tour.asp.
Alzheimer’s Association. Brain plaques and Tangles - Alzheimer’s association. Retrieved May 1, 2016a, from Alzheimer’s Association, https://www.alz.org/braintour/plaques_tangles.asp.
Alzheimer’s Association. Healthy brain versus Alzheimer’s brain. Retrieved May 1, 2016c, from Alzheimer’s Association, https://www.alz.org/braintour/healthy_vs_alzheimers.asp.
Winslow, B. T., Onysko, M. K., Stob, C. M., & Hazlewood, K. A. (2011). Treatment of Alzheimer Disease. American Academy of Family Physicians, 83 (12), 1403–1412..
Inacio, P. (2014, November 3). Tau protein leads to neuronal death in Alzheimer’s. Retrieved January 17, 2017, from Alzheimer’s News Today, https://alzheimersnewstoday.com/2014/11/03/tau-protein-leads-to-neuronal-death-in-alzheimers/.
Feller, S. (2016, March 3). Early diagnosis, staging of Alzheimer’s disease seen in PET scans. Retrieved August 5, 2016, from United Press International, http://www.upi.com/Health_News/2016/03/03/Early-diagnosis-staging-of-Alzheimers-disease-seen-in-PET-scans/1701457010215/.
Ogbru, O. (2016, January 22). Tacrine: Side effects and Dosing. Retrieved August 11, 2016, from MedicineNet.com, http://www.medicinenet.com/tacrine/article.htm.
Mayo Clinic Staff (2014). Early-onset Alzheimer’s: When symptoms begin before age 65 early-onset Alzheimer’s: When symptoms begin before age 65. Mayoclinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/ART-20048356.
Bird, T. D. (2012). Early-Onset Familial Alzheimer Disease. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1236/.
Kamboh, M. I. (2004). Molecular genetics of late-onset Alzheimer’s disease. Annals of Human Genetics, 68 (4), 381–404. doi:10.1046/j.1529-8817.2004.00110.x.
Lava, N. (2005, January 29). Alzheimer’s disease stages. Retrieved October 4, 2016, from WebMD, http://www.webmd.com/alzheimers/guide/alzheimers-disease-stages.
N/A. (2015). The 7 stages of Alzheimer’s disease. Retrieved October 4, 2016, from Memory Study, http://memorystudy.org/alzheimers_stages.htm.
N/A. (2004). Genes and environment affect Alzheimer’s risk. Retrieved October 4, 2016, from WebMD, http://www.webmd.com/alzheimers/news/20040721/genes-environment-affect-alzheimers-risk?page=2.
Calderón-Garcidueñas, L., Franco-Lira, M., Torres-Jardón, R., Henriquez-Roldán, C., Barragán-Mejía, G., Valencia-Salazar, G., … Reed, W. (2007). Pediatric respiratory and systemic effects of chronic air pollution exposure: Nose, lung, heart, and brain pathology. Toxicol Pathol, 35 (1), 154–162. doi:10.1080/01926230601059985.
Block, M. L., & Calderón-Garcidueñas, L. (2009). Air pollution: Mechanisms of Neuroinflammation & CNS disease. Trends In Neuroscience, 32 (9), 506–516. doi:10.1016/j.tins.2009.05.009.
Burdick, S. (2008). Environmental Threats to Healthy Aging: Environmental Factors in the Development of Dementia. Retrieved from http://www.agehealthy.org/pdf/chap7_0926.pdf.
Block, M. L., Elder, A., Auten, R. L., Bilbo, S. D., Chen, H., Chen, J.-C., … Wright, R. O. (2012). The outdoor air pollution and brain health workshop. Neurotoxicology, 33 (5), 972–984. doi:10.1016/j.neuro.2012.08.014.
Porterfield, S. P., & Hendry, L. B. (1998). Impact of Pcbs on thyroid hormone directed brain development. Toxicol Ind Health, 14 (1-2), 103–120. doi:10.1177/074823379801400109.
Baldi, I., Filleul, L., Mohammed-Brahim, B., Fabrigoule, C., Dartigues, J.-F., Schwall, S., … Brochard, P. (2001). Neuropsychologic effects of long-term exposure to pesticides: Results from the french Phytoner study. Environmental Health Perspectives, 109 (8), 839–844. doi:10.1289/ehp.01109839.
Basha, M. R., Wei, W., Bakheet, S. A., Benitez, N., Siddiq, H. K., Ge, Y. W., Lahiri, D. K., Zawia, N. H. (2005). The fetal basis of Amyloidogenesis: Exposure to lead and latent Overexpression of Amyloid precursor protein and -Amyloid in the aging brain. Journal of Neuroscience, 25 (4), 823–829. doi:10.1523/jneurosci.4335-04.2005.
Judd, N. (2014, July 1). What is Alzheimer’s disease? Retrieved October 8, 2016, from Alzheimer’s Society, https://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=100.
N/A. (2016). Vascular dementia | signs, symptoms, & diagnosis. Retrieved October 8, 2016, from Alzheimer’s Association, https://www.alz.org/dementia/vascular-dementia-symptoms.asp.
Borruat, F.-X. (2013). Posterior cortical atrophy: Review of the recent literature. Current Neurology and Neuroscience Reports, 13 (12), 406. doi:10.1007/s11910-013-0406-8.
Cacabelos, R., & Torrellas, C. (2014). Epigenetic drug discovery for Alzheimer’s disease. Expert Opinion on Drug Discovery, 9 (9), 1059–1086. doi:10.1517/17460441.2014.930124.
Alzheimer’s Association (2016). 2016 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 12 (4), 459–509. doi:10.1016/j.jalz.2016.03.001.
Shih, R. A., Hu, H., Weisskopf, M. G., & Schwartz, B. S. (2006). Cumulative lead dose and cognitive function in adults: A review of studies that measured Both blood lead and bone lead. Environmental Health Perspectives, 115 (3), 483–492. doi:10.1289/ehp.9786.
Weisskopf, M. G., Proctor, S. P., Wright, R. O., Schwartz, J., Spiro, A., Sparrow, D., … Hu, H. (2007). Cumulative lead exposure and cognitive performance among elderly men. Epidemiology, 18 (1), 59–66. doi:10.1097/01.ede.0000248237.35363.29.
Basha, M. R., Murali, M., Siddiq, H. K., Ghosal, K., Siddiq, O. K., Lashuel, H. A., … Zawia, N. H. (2005). Lead (Pb) exposure and its effect on APP proteolysis and A aggregation. The FASEB Journal, 19 (14), 2083–2084. doi:10.1096/fj.05-4375fje.
Wang, Y., & Ha, Y. (2004). The x-ray structure of an Antiparallel Dimer of the human Amyloid precursor protein E2 domain. Molecular Cell, 15 (3), 343–353. doi:10.1016/j.molcel.2004.06.037.
Dahms, S. O., Hoefgen, S., Roeser, D., Schlott, B., Guhrs, K.., & Than, M. E. (2010). Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein. Proceedings of the National Academy of Sciences, 107 (12), 5381–5386. doi:10.1073/pnas.0911326107.
N/A. (2012, July 13). Mutations. Retrieved October 13, 2016, from ALZ Forum, http://www.alzforum.org/mutation/app-a673t-icelandic.
De Strooper, B., & Voet, T. (2012). Alzheimer’s disease: A protective mutation. Nature, 488 (7409), 38–39. doi:10.1038/488038a.
Mayo Clinic Staff. (2016, January 26). Alzheimer's: Is it in your genes? - Mayo Clinic. Retrieved October 23, 2016, from http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/ART-20046552?pg=2.
N/A. (2013, March 13). Genetic Risk Factors: Apolipoprotein E. Retrieved October 20, 2016, from http://dshs.texas.gov/alzheimers/apolipo.shtm.
Corder, E., Saunders, A., Strittmatter, W., Schmechel, D., Gaskell, P., Small, G., … Pericak-Vance, M. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Reports, 261 (5123), 921–923. doi:10.1126/science.8346443.
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., … Pericak-Vance, M. A. (1994). Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease - nature genetics. Nature Genetics, 7 (2), 180–184. doi:10.1038/ng0694-180.
n/a. (2016, February 25). Avraham pharmaceuticals closes an additional investment round of approximately $4.0 Million. Retrieved October 24, 2016, from Avraham Pharma, http://www.avphar.com/avraham-pharmaceuticals-closes-an-additional-investment-round-of-approximately-4-0-million/.
Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010). A Meta-Analysis of Cytokines in Alzheimer’s disease. Biological Psychiatry, 68 (10), 930–941. doi:10.1016/j.biopsych.2010.06.012.
Sirviö, J. (1999). Strategies that support declining Cholinergic Neurotransmission in Alzheimer’s disease patients. Gerontology, 45 (1), 3–14. doi:10.1159/000052759.
Bartus, R., Dean, R., Beer, B., & Lippa, A. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Articles, 217 (4558), 408–414. doi:10.1126/science.7046051.
Hökfelt, T. (2009). Looking at neurotransmitters in the microscope. Progress in neurobiology., 90 (2), 101–18. doi:10.1016/j.pneurobio.2009.10.005.
Bowen, D. M., Smith, C. B., White, P., & Davison, A. N. (1976). Neurotransmitter-Related Enzymes And Indices Of Hypoxia in Senile Dementia and other Abiotrophies. Brain, 99, 459–496. doi:10.1093/brain/99.3.459.
Kish, S. J., Robitaille, Y., El-Awar, M., Deck, H. N., Simmons, J., Schut, L., … Freedman, M. (1989). Non-Alzheimer-type pattern of brain cholineacetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy. Annals of Neurology, 26 (3), 362–367. doi:10.1002/ana.410260309.
Davis, K. L., Mohs, R. C., Marin, D., Purohit, D. P., Perl, D. P., Lantz, M., … Haroutunian, V. (1999). Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA, 281 (15), 1401–1406. doi:10.1001/jama.281.15.1401.
Tiraboschi, P., Hansen, L. A., Alford, M., Masliah, E., Thal, L. J., & Corey–BloomJ (2000). The decline in synapses and cholinergic activity is asynchronous in Alzheimer’s disease. Neurology, 55 (9), 1278–1283. doi:10.1212/WNL.55.9.1278.
Ikonomovic, M. D., Mufson, E. J., Wuu, J., Cochran, E. J., Bennett, D. A., & DeKosky, S. T. (2003). Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: Correlation with Alzheimer’s neuropathology. Journal of Alzheimer’s Disease, 5 (1), 39–48. Retrieved from http://content.iospress.com/articles/journal-of-alzheimers-disease/jad00225.
Chen, Z., & Zhong, C. (2014). Oxidative stress in Alzheimer’s disease. Neuroscience Bulletin, 30 (2), 271–281. doi:10.1007/s12264-013-1423-y.
De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., & Van Leuven, F. (1998b). Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature, 391 (6665), 387–390. doi:10.1038/34910.
Cacabelos, R., & Torrellas, C. (2014). Epigenetic drug discovery for Alzheimer’s disease. Expert Opinion on Drug Discovery, 9 (9), 1059–1086. doi:10.1517/17460441.2014.930124.
Adwan, L., & Zawia, N. H. (2013). Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease. Pharmacology & Therapeutics, 139 (1), 41–50. doi:10.1016/j.pharmthera.2013.03.010.
Yang, W., Chauhan, A., Mehta, S., Mehta, P., Gu, F., & Chauhan, V. (2014). Trichostatin A increases the levels of plasma gelsolin and amyloid beta-protein in a transgenic mouse model of Alzheimer’s disease. Life Sciences, 99 (1-2), 31–36. doi:10.1016/j.lfs.2014.01.064.
Chai, G.-S., Jiang, X., Ni, Z.-F., Ma, Z.-W., Xie, A.-J., Cheng, X.-S., … Liu, G.-P. (2013). Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. Journal of Neurochemistry, 124 (3), 388–396. doi:10.1111/jnc.12094.
Mishra, S., & Palanivelu, K. (2008). The effect of curcumin (turmeric) on Alzheimer′s disease: An overview. Annals of Indian Academy of Neurology, 11 (1), 13. doi:10.4103/0972-2327.40220.
Green, K. N., Steffan, J. S., Martinez-Coria, H., Sun, X., Schreiber, S. S., Thompson, L. M., & LaFerla, F. M. (2008). Nicotinamide restores Cognition in Alzheimer’s disease transgenic mice via a mechanism involving Sirtuin inhibition and selective reduction of Thr231-Phosphotau. Journal of Neuroscience, 28 (45), 11500–11510. doi:10.1523/jneurosci.3203-08.2008.
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., … Pasinetti, G. M. (2013). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiology of Aging, 34 (6), 1581–1588. doi:10.1016/j.neurobiolaging.2012.12.005.
Block, W. (n.d). Nicotinamide restores Cognition in Alzheimer’s disease. Retrieved December 7, 2016, from Life Enhancement, http://www.life-enhancement.com/magazine/article/2049-nicotinamide-restores-cognition-in-alzheimers-disease.
Gene editing. (n.d.) Gale Encyclopedia of Medicine. (2008). Retrieved November 20 2016 from http://medical-dictionary.thefreedictionary.com/Gene+editing.
Hitti, M. (2005). Alzheimer’s Gene Therapy slows mental decline. Retrieved November 20, 2016, from WebMD, http://www.webmd.com/alzheimers/news/20050425/alzheimers-gene-therapy-slows-mental-decline.
Katsouri, L., Lim, Y. M., Blondrath, K., Eleftheriadou, I., Lombardero, L., Birch, A. M., … Sastre, M. (2016). PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model. Proceedings of the National Academy of Sciences, 113 (43), 12292–12297. doi:10.1073/pnas.1606171113.
Sadigh-Eteghad, S., Majdi, A., Mahmoudi, J., Golzari, S. E. J., & Talebi, M. (2016). Astrocytic and microglial nicotinic acetylcholine receptors: An overlooked issue in Alzheimer’s disease. Journal of Neural Transmission, 123 (12), 1359–1367. doi:10.1007/s00702-016-1580-z.
n/a. (2011). AlzGene - Top Results. Retrieved December 14, 2016, from Alzforum, http://www.alzgene.org/TopResults.asp.
n/a. (2016a). BIN1 bridging integrator 1 [Homo sapiens (human)]. Retrieved from https://www.ncbi.nlm.nih.gov/gene/274.
Ikeda, M. (1996). [Presenilin-1 (S182) causative gene of early-onset familial Alzheimer’s disease]. Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme., 41 (10), 1441–7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8741394
Roses, A., & Saunders, A. (1994). APOE is a major susceptibility gene for Alzheimer’s disease. Current opinion in biotechnology., 5 (6), 663–7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7765750.
Alagiakrishnan, K., Gill, S. S., & Fagarasanu, A. (2012). Genetics and epigenetics of Alzheimer’s disease. Postgraduate Medical Journal, 88 (1043), 522–529. doi:10.1136/postgradmedj-2011-130363.
Proitsi, P., Lee, S. H., Lunnon, K., Keohane, A., Powell, J., Troakes, C., … Hodges, A. (2014). Alzheimer’s disease susceptibility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood. Neurobiology of Aging, 35 (2), 279–290. doi:10.1016/j.neurobiolaging.2013.08.002.
n/a. (2016b, December 6). Clusterin [Homo sapiens (human)]. Retrieved December 15, 2016, from National Center for Biotechnology Information, https://www.ncbi.nlm.nih.gov/gene/1191.
Zhou, X.-W., Tanila, H., Liu, R., Winblad, B., & Pei, J.-J. (2006). P3-301. Alzheimer’s & Dementia, 2 (3), S463–S464. doi:10.1016/j.jalz.2006.05.1571.
Baki, L., Shioi, J., Wen, P., Shao, Z., Schwarzman, A., Gama-Sosa, M., … Robakis, N. K. (2004). PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: Effects of FAD mutations. The EMBO Journal, 23 (13), 2586–2596. doi:10.1038/sj.emboj.7600251.
Buée, L., Bussière, T., Buée-Scherrer, V., Delacourte, A., & Hof, P. R. (2000b). Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Research Reviews, 33 (1), 95–130. doi:10.1016/S0165-0173(00)00019-9.
Hernandez, F., & Avila, J. (2007). Tauopathies. Cellular and Molecular Life Sciences, 64 (17), 2219–2233. doi: DOI 10.1007/s00018-007-7220-x.
Mattson, M., Fu, W., Waeg, G., & Uchida, K. (1997). 4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau. Neuroreport., 8 (9-10), 2275–81. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9243625.
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