Phytochemicals in Alzheimer disease, the development of clinical trials
Open accessAbstract
Polyphenolics and other phytochemicals may have a role in the prevention or treatment of Alzheimer disease. Targets of therapy in Alzheimer disease include neurotransmitter deficits, beta amyloid neurotoxicity, oxidative damage, and inflammation, to name a few. Challenges to the development of phytochemical and other neuroprotectant therapy in Alzheimer disease include the inability to measure pathology in living patients and the challenge of detecting modification of an indolent disease course. These challenges are partially surmounted by the use of animal models and of biomarkers of disease. This review describes currently available animal models and biomarkers and surveys clinical trials of phytochemical therapies that are recently completed or currently under way. Both animal studies and clinical trials of Ginkgo biloba are described, as well as a trial of Uncaria tomentosa that has not been previously reported.
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Cholinergic dysfunction, amyloid-β neurotoxicity, oxidative damage and inflammation have been targeted for treatment of Alzheimer's disease but with limited success.
“Cholinergic dysfunction, amyloid-β neurotoxicity, oxidative damage and inflammation have been targeted for treatment of AD but with limited success [23,24].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [23]
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516 · see citing works
Perry, E., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P., & Perry, R. H. (1978) · British medical journal · doi:10.1136/bmj.2.6150.1457 · Cited by 2,043 · see citing works
Lim, G. P., Chu, T., Yang, F., Beech, W., Frautschy, S. A., & Cole, G. M. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-21-08370.2001 · Cited by 1,530 · see citing works
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment
Jack, C. R., Petersen, R. C., Xu, Y. C., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Waring, S. C., Tangalos, E. G., & Kokmen, E. (1999) · Neurology · doi:10.1212/wnl.52.7.1397 · Cited by 1,404 · see citing works
Morrow, J. D., Frei, B. B., Longmire, A. W., Gaziano, J. M., Lynch, S. M., Shyr, Y., Strauss, W., Oates, J. A., & Roberts, L. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505043321804 · Cited by 1,340 · see citing works
A Placebo-Controlled, Double-blind, Randomized Trial of an Extract of Ginkgo Biloba for Dementia
Le Bars, P. L. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03550160047037 · Cited by 966 · see citing works
Shoghi, K. I., Small, G. W., Agdeppa, E. D., Kepe, V., Ercoli, L. M., Siddarth, P., Read, S., Satyamurthy, N., Petrič, A., Huang, S., et al. (2002) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200201000-00004 · Cited by 774 · see citing works
IRIZARRY, M. C., MCNAMARA, M., FEDORCHAK, K., HSIAO, K., & HYMAN, B. T. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199709000-00002 · Cited by 649 · see citing works
Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia
Jack, C. R., Dickson, D. W., Parisi, J. E., Xu, Y. C., Cha, R. H., O’Brien, P. C., Edland, S. D., Smith, G. E., Boeve, B. F., Tangalos, E. G., et al. (2002) · Neurology · doi:10.1212/wnl.58.5.750 · Cited by 610 · see citing works
Microglial response to amyloid plaques in APPsw transgenic mice.
Frautschy, S. A., Yang, F., Irrizarry, M., Hyman, B. T., Saido, T. C., Hsiao, K., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 592 · see citing works
Increase of Brain Oxidative Stress in Mild Cognitive Impairment
Praticò, D., Clark, C. M., Liun, F., Lee, V., & Trojanowski, J. Q. (2002) · Archives of Neurology · doi:10.1001/archneur.59.6.972 · Cited by 587 · see citing works
The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease
Oken, B., Storzbach, D. M., & Kaye, J. A. (1998) · Archives of Neurology · doi:10.1001/archneur.55.11.1409 · Cited by 585 · see citing works
Self-citationThe isoprostanes: Unique bioactive products of lipid peroxidation
Morrow, J. D., & Roberts, L. J. (1997) · Progress in Lipid Research · doi:10.1016/s0163-7827(97)00001-5 · Cited by 556 · see citing works
Amyloid‐β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative Stress
Smith, M. A., Hirai, K., Hsiao, K., Pappolla, M. A., Harris, P. L. R., Siedlak, S. L., Tabaton, M., & Perry, G. L. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052212.x · Cited by 547 · see citing works
Aging renders the brain vulnerable to amyloid β-protein neurotoxicity
Guela, C., Wu, C.-K., Saroff, D., Lorenzo, A., Yuan, M., & Yankner, B. A. (1998) · Nature Medicine · doi:10.1038/nm0798-827 · Cited by 520 · see citing works
γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in?
Sisodia, S. S., & St George-Hyslop, P. H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn785 · Cited by 512 · see citing works
Montine, T. J., Neely, M. D., Quinn, J. F., Beal, M. F., Markesbery, W. R., Roberts, L. J., & Morrow, J. D. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00807-9 · Cited by 449 · see citing works
Self-citationModification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior
Mattson, M. P., Chan, S. L., & Duan, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00004.2002 · Cited by 438 · see citing works
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406 · see citing works
Kaye, J. A., Swihart, T., Howieson, D., Dame, A., Moore, M. M., Karnos, T., Camicioli, R., Ball, M., Oken, B., & Sexton, G. (1997) · Neurology · doi:10.1212/wnl.48.5.1297 · Cited by 399 · see citing works
Self-citationInhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761
Luo, Y., Smith, J. V., Paramasivam, V., Burdick, A. J., Curry, K. J., Buford, J. P., Khan, I. A., Netzer, W. J., Xu, H., & Butko, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182425199 · Cited by 399 · see citing works
Bastianetto, S., Ramassamy, C., Doré, S., Christen, Y., Poirier, J., & Quirion, R. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00069.x · Cited by 378 · see citing works
Kanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440108 · Cited by 340 · see citing works
Correlation between rates of brain atrophy and cognitive decline in AD
Fox, N. C., Scahill, R. I., Crum, W. R., & Rossor, M. N. (1999) · Neurology · doi:10.1212/wnl.52.8.1687 · Cited by 338 · see citing works
Evidence for glial-mediated inflammation in aged APPSW transgenic mice
Benzing, W. C., Wujek, J. R., Ward, E. K., Shaffer, D. J., Ashe, K. H., Younkin, S. G., & Brunden, K. R. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00065-2 · Cited by 298 · see citing works
Changes in premorbid brain volume predict Alzheimer’s disease pathology
Silbert, L. C., Quinn, J. F., Moore, M. M., Corbridge, E., Ball, M. J., MURDOCH, G. H., Sexton, G. J., & Kaye, J. A. (2003) · Neurology · doi:10.1212/01.wnl.0000079053.77227.14 · Cited by 280 · see citing works
Self-citationLaakso, M. P., Soininen, H. S., Partanen, K. P. L., Lehtovirta, M., Hallikainen, M., Hänninen, T., Helkala, E.-L., Vainio, P. A., & Riekkinen, P. J. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00006-2 · Cited by 265 · see citing works
Increased CSF F 2 -isoprostane concentration in probable AD
Montine, T. J., Beal, M. F., Cudkowicz, M., O’Donnell, H., Margolin, R. A., McFarland, L. L., Bachrach, A., Zackert, W. E., Roberts, L. J., & Morrow, J. D. (1999) · Neurology · doi:10.1212/wnl.52.3.562 · Cited by 251 · see citing works
Self-citationMehta, P. D., Pirttilä, T., Patrick, B. A., Barshatzky, M., & Mehta, S. P. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01754-2 · Cited by 230 · see citing works
Stackman, R. W., Eckenstein, F., Frei, B., Kulhanek, D., Nowlin, J., & Quinn, J. F. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00399-6 · Cited by 230 · see citing works
Self-citationFruit Polyphenolics and Brain Aging
Galli, R. L., Shukitt‐Hale, B., Youdim, K. A., & Joseph, J. A. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02089.x · Cited by 199 · see citing works
Alzheimer's Disease Assessment Scale (ADAS).
Mohs, R. C., & Cohen, L. (1988) · PubMed · Cited by 195 · see citing works
Sandoval, M., Okuhama, N. N., Zhang, X.-J., Condezo‐Hoyos, L., Lao, J., Angeles, F. M., Musah, R. A., Bobrowski, P. J., & Miller, M. J. S. (2002) · Phytomedicine · doi:10.1078/0944-7113-00117 · Cited by 189 · see citing works
High Levels of Circulating Aβ42 Are Sequestered by Plasma Proteins in Alzheimer's Disease
Kuo, Y., Emmerling, M. R., Lampert, H. C., Hempelman, S. R., Kokjohn, T. A., Woods, A. S., Cotter, R. J., & Roher, A. E. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0552 · Cited by 182 · see citing works
Yao, Z., Drieu, K., & Papadopoulos, V. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03131-0 · Cited by 181 · see citing works
Peripheral F2‐isoprostanes and F4‐neuroprostanes are not increased in Alzheimer's disease
Montine, T. J., Quinn, J. F., Milatović, D., Silbert, L. C., Dang, T. N. T., Sanchez, S. C., Terry, E. S., Roberts, L. J., Kaye, J. A., & Morrow, J. D. (2002) · Annals of Neurology · doi:10.1002/ana.10272 · Cited by 156 · see citing works
Self-citationAmyloid β protein in plasma from patients with sporadic Alzheimer's disease
Tamaoka, A., Fukushima, T., Sawamura, N., Ishikawa, K., Oguni, E., Komatsuzaki, Y., & Shoji, S. (1996) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(96)00143-8 · Cited by 154 · see citing works
Emre, M., Geula, C., Ransil, B., & Mesulam, M. M. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90055-3 · Cited by 125 · see citing works
Montine, T. J., Kaye, J. A., Montine, K. S., McFarland, L. L., Morrow, J. D., & Quinn, J. F. (2001) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2001-125-0510-cfataf · Cited by 121 · see citing works
Self-citationTransgenic mice expressing Alzheimer amyloid precursor proteins
Hsiao, K. (1998) · Experimental Gerontology · doi:10.1016/s0531-5565(98)00045-x · Cited by 119 · see citing works
Montine, T. J., Markesbery, W. R., Zackert, W. E., Sanchez, S. C., Roberts, L. J., & Morrow, J. D. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65185-1 · Cited by 116 · see citing works
Self-citationβ-Amyloid neurotoxicity: A discussion of in vitro findings
Cotman, C. W., Pike, C. J., & Copani, A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90060-b · Cited by 112 · see citing works
Imaging Amyloid-β Deposits In Vivo
Bacskai, B. J., Klunk, W. E., Mathis, C. A., & Hyman, B. T. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200209000-00001 · Cited by 106 · see citing works
Harkany, T., Hortobágyi, T., Sasvári, M., Kónya, C., Penke, B., Luiten, P. G. M., & Nyakas, C. J. (1999) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(99)00058-5 · Cited by 97 · see citing works
Effects of an extract of Ginkgo biloba on learning and memory in mice
Winter, E. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90597-u · Cited by 89 · see citing works
Advances in the detection of Alzheimer's disease-use of cerebrospinal fluid biomarkers.
Sjögren, M., Andreasen, N., & Blennow, K. (2003) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/s0009-8981(03)00121-9 · Cited by 88 · see citing works
Apolipoprotein E4 promotes the early deposition of Aβ42 and then Aβ40 in the elderly
Walker, L. C., Pahnke, J., Madauss, M., Vogelgesang, S., Pahnke, A., Herbst, E. W., Stausske, D., Walther, R., Kessler, C., & Warzok, R. (2000) · Acta Neuropathologica · doi:10.1007/s004010051190 · Cited by 81 · see citing works
Hernandez, D., Sugaya, K., Qu, T., McGowan, E., Duff, K., & McKinney, M. (2001) · Neuroreport · doi:10.1097/00001756-200105250-00018 · Cited by 73 · see citing works
Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment
de Leon, M. J., Segal, S., Tarshish, C. Y., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Convit, A. J., Caraos, C., Rusinek, H., Tsui, W., et al. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)01038-8 · Cited by 70 · see citing works
Micronutrients in Cancer Chemoprevention
Greenwald, P., Milner, J. A., Anderson, D. E., & McDonald, S. S. (2002) · Cancer and Metastasis Reviews · doi:10.1023/a:1021202709003 · Cited by 67 · see citing works
Barkats, M., Venault, P., Christen, Y., & Cohen‐Salmon, C. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00915-5 · Cited by 63 · see citing works
Abdel-Fattah, M. A. F., Matsumoto, K., Tabata, K., Takayama, H., Kitajima, M., Aimi, N., & Watanabe, H. (2000) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357001777612 · Cited by 58 · see citing works
Interspecies Scaling: Predicting Oral Clearance in Humans
Mahmood, I. (2002) · American Journal of Therapeutics · doi:10.1097/00045391-200201000-00008 · Cited by 33 · see citing works
Pirttilä, T., Koivisto, K. J., Mehta, P. D., Reinikainen, K. J., Kim, K. S., Kilkku, O., Heinonen, E. H., Soininen, H. S., Riekkinen, P. J., & Wı́sniewski, H. M. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00381-4 · Cited by 31 · see citing works
MRS in relation to hippocampal volume in the oldest old
Spencer, D. C., Zitzelberger, T., Spielman, D. M., & Kaye, J. A. (2003) · Neurology · doi:10.1212/01.wnl.0000052822.22994.86 · Cited by 13 · see citing works
Self-citationTransderm-induced psychosis in Parkinson's disease
Quinn, N. P., Minagar, A., Shulman, L. M., & Weiner, W. J. (2000) · Neurology · doi:10.1212/wnl.54.9.1877 · Cited by 2 · see citing works
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Mehla, J., Gupta, P., Pahuja, M., Diwan, D., & Diksha, D. (2020) · Brain Sciences · doi:10.3390/brainsci10120964 · Cited by 108 · see citing works
“Cholinergic dysfunction, amyloid-β neurotoxicity, oxidative damage and inflammation have been targeted for treatment of AD but with limited success [23,24].”
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Gomes, N. G. M., Campos, M. G., Órfão, J., & Ribeiro, C. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.07.033 · Cited by 99 · see citing works
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Man, S. C., Durairajan, S. S. K., Kum, W. F., Lu, J., Huang, J. D., Cheng, C. F., Chung, V. C., Xu, M., & Li, M. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14209 · Cited by 46 · see citing works
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Abourashed, E. A., Abraha, A., Khan, S. I., McCants, T., & Awan, S. (2015) · Natural Product Communications · doi:10.1177/1934578x1501000923 · Cited by 11 · see citing works
Guthrie, O. W., & Li, Y. (2023) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2885 · Cited by 3 · see citing works
Perspective and Direction for Future Research on Phytochemicals in Neurological Disorders
Farooqui, A. A. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3804-5_11 · Cited by 1 · see citing works
CSF biomarkers of AD: monitoring therapeutic targets N eurodegenerative Disease
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- Authors
- Quinn, J., Kaye, J., Montine, T., & Stackman, R.
- Affiliations
- Oregon Health & Science University (US)
- University of Washington Medical Center (US)
- Corresponding author
- Quinn, Joseph
- Venue
- Pharmaceutical Biology
- Publisher
- Informa UK Limited
- Published
- 2004-01
- Volume
- 42
- Issue
- sup1
- Pages
- 64-73
- ISSN
- 0925-1618 (ISSN-L)
- 1388-0209
- 1744-5116
- OpenAlex
- W2062668918
- Cited by
- 8
- References
- 62
- Citations by year
- 2023: 2 · 2020: 1 · 2015: 1 · 2012: 1
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmaceutical Biology (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
- Keywords
- Alzheimer's disease, phytochemicals, polyphenols, Ginkgo biloba, Uncaria tomentosa, neuroprotective therapy, biomarkers, clinical trials, amyloid-beta toxicity, oxidative damage, inflammation, neurotransmitter deficits
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