Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: Link to brain reductions in acetylcholine
Abstract
Reduced glucose utilization and energy metabolism occur early in the course of Alzheimer's disease (AD) and correlate with impaired cognition. Glucose utilization and energy metabolism are regulated by insulin and insulin-like growth factor I (IGF-I), and correspondingly, studies have shown that cognitive impairment may be improved by glucose or insulin administration. Recently, we demonstrated significantly reduced levels of insulin and IGF-I polypeptide genes and their corresponding receptors in advanced AD relative to aged control brains. The abnormalities in gene expression were accompanied by impaired survival signaling downstream through PI3 kinase-Akt. The present work characterizes the abnormalities in insulin and IGF gene expression and receptor binding in brains with different Braak stage severities of AD. Realtime quantitative RT-PCR analysis of frontal lobe tissue demonstrated that increasing AD Braak Stage was associated with progressively reduced levels of mRNA corresponding to insulin, IGF-I, and IGF-II polypeptides and their receptors, tau, which is regulated by insulin and IGF-I, and the Hu D neuronal RNA binding protein. In contrast, progressively increased levels of amyloid beta protein precursor (AbetaPP), glial fibrillary acidic protein, and the IBA1/AIF1 microglial mRNA transcripts were detected with increasing AD Braak Stage. Impairments in growth factor and growth factor receptor expression and function were associated with increasing AD Braak stage dependent reductions in insulin, IGF-I, and IGF-II receptor binding, ATP levels, and choline acetyltransferase (ChAT) expression. Further studies demonstrated that: 1) ChAT expression increases with insulin or IGF-I stimulation; 2) ChAT is expressed in insulin and IGF-I receptor-positive cortical neurons; and 3) ChAT co-localization in insulin or IGF-I receptor-positive neurons is reduced in AD. Together, these data provide further evidence that AD represents a neuro-endocrine disorder that resembles a unique form of diabetes mellitus (? Type 3) and progresses with severity of neurodegeneration.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Higher Iba1 was noted in the Alzheimer's disease frontal cortex in four studies, was the same as control in three others, and was lower in the white matter of the frontal lobe in one study.
“Higher Iba1 was noted in the AD frontal cortex in four studies,20, 63, 64, 68 but was the same as control in three others32, 70, 74 and lower in the white matter of the frontal lobe in one study.32”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [64]
Brain insulin signaling declines with age, and this is the primary risk factor for Alzheimer's disease.
“Brain insulin signaling declines with age (Frolich et al., 1998; , 1999; Hoyer, 1998; Rivera et al., 2005), the primary risk factor for AD.”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Rivera et al., 2005
Levels of brain insulin and insulin receptors are lower in Alzheimer's disease.
“levels of brain insulin and insulin receptors (IRs) are lower in AD (Frolich et al., 1998; Rivera et al., 2005).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Rivera et al., 2005
Cites
Regulation of neuronal survival by the serine-threonine protein kinase Akt
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E. (1997) · Science · doi:10.1126/science.275.5300.661 · Cited by 2,436 · see citing works
Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes
Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L., Dull, T. J., Gray, A., Coussens, L. M., Liao, Y.-C., Tsubokawa, M., et al. (1985) · Nature · doi:10.1038/313756a0 · Cited by 2,251 · see citing works
Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction
Burgering, B. M. T., & Coffer, P. J. (1995) · Nature · doi:10.1038/376599a0 · Cited by 2,113 · see citing works
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703 · see citing works
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574 · see citing works
HYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542 · see citing works
Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J., & Dedhar, S. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.19.11211 · Cited by 1,149 · see citing works
Kulik, G., Klippel, A., & Weber, M. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1595 · Cited by 1,033 · see citing works
Imai, Y., Ibata, I., Ito, D., Ohsawa, K., & Kohsaka, S. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1112 · Cited by 872 · see citing works
Insulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation
Qiu, W. Q., Walsh, D. M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M. B., Rosner, M. R., Safavi, A., Hersh, L. B., & Selkoe, D. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32730 · Cited by 812 · see citing works
The role of inflammation in Alzheimer’s disease
Tuppo, E. E., & Arias, H. R. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.07.009 · Cited by 734 · see citing works
Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells
White, M. F., Maron, R., & Kahn, C. R. (1985) · Nature · doi:10.1038/318183a0 · Cited by 660 · see citing works
Ito, D., Tanaka, K., Suzuki, S., Dembo, T., & Fukuuchi, Y. (2001) · Stroke · doi:10.1161/01.str.32.5.1208 · Cited by 593 · see citing works
Szabo, A., Dalmau, J., Manley, G., Rosenfeld, M., Wong, E., Henson, J., Posner, J. B., & Furneaux, H. M. (1991) · Cell · doi:10.1016/0092-8674(91)90184-z · Cited by 553 · see citing works
de la Monte, S. M., & Wands, J. R. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-7106 · Cited by 552 · see citing works
Alzheimer's β-Amyloid Peptides Compete for Insulin Binding to the Insulin Receptor
Xie, L., Helmerhorst, E., Taddei, K., Plewright, B., van Bronswijk, W., & Martins, R. N. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-j0001.2002 · Cited by 542 · see citing works
Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q
Bertram, L., Blacker, D., Mullin, K., Keeney, D. B., Jones, J., Basu, S., Yhu, S., McInnis, M. G., Go, R. C. P., Vekrellis, K., et al. (2000) · Science · doi:10.1126/science.290.5500.2302 · Cited by 519 · see citing works
Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert, M., Brazil, D. P., Burks, D. J., Kushner, J. A., Ye, J., Flint, C. L., Farhang-Fallah, J., Dikkes, P., Warot, X. M., Rio, C., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07084.2003 · Cited by 488 · see citing works
Pleiotropic Insulin Signals are Engaged by Multisite Phosphorylation of IRS-1
Sun, X., Crimmins, D. L., Myers, M. G., Miralpeix, M., & White, M. F. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.12.7418 · Cited by 466 · see citing works
Glucose metabolism and insulin receptor signal transduction in Alzheimer disease
Hoyer, S. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.049 · Cited by 436 · see citing works
Diagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00062-6 · Cited by 410 · see citing works
Blasko, I., Stampfer‐Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P., & Grubeck‐Loebenstein, B. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00101.x · Cited by 374 · see citing works
Role for neuronal insulin resistance in neurodegenerative diseases
Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Kustermann, E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308724101 · Cited by 339 · see citing works
Myers, M. G., Sun, X. J., & White, M. F. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90007-8 · Cited by 315 · see citing works
Farris, W., Mansourian, S., Leissring, M. A., Eckman, E. A., Bertram, L., Eckman, C. B., Tanzi, R. E., & Selkoe, D. J. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63229-4 · Cited by 269 · see citing works
Craft, S., Asthana, S., Cook, D. G., Baker, L. D., Cherrier, M. M., Purganan, K., Wait, C., Petrova, A., Latendresse, S. J., Watson, G. S., et al. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00087-2 · Cited by 255 · see citing works
Pérez, A., Morelli, L., Cresto, J. C., & Castaño, E. M. (2000) · Neurochemical Research · doi:10.1023/a:1007527721160 · Cited by 240 · see citing works
Lam, K., Carpenter, C. L., Ruderman, N. B., Friel, J., & Kelly, K. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32042-2 · Cited by 232 · see citing works
Neuropathology of Alzheimer’s disease: a critical update
Jellinger, K. A., & Bancher, C. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-7508-8_8 · Cited by 231 · see citing works
Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer's disease
de la Monte, S. M., Luong, T., Neely, T. R., Robinson, D., & Wands, J. R. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780140 · Cited by 227 · see citing works
The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update
Hoyer, S. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200028 · Cited by 206 · see citing works
Craft, S., Asthana, S., Schellenberg, G. D., Baker, L. D., Cherrier, M. M., Boyt, A., Martins, R. N., Raskind, M. A., Peskind, E. R., & Plymate, S. R. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06371.x · Cited by 191 · see citing works
MCDERMOTT, J. R., & GIBSON, A. M. (1997) · Neurochemical Research · doi:10.1023/a:1027325304203 · Cited by 184 · see citing works
Neuroinflammatory perspectives on the two faces of Alzheimer?s disease
Eikelenboom, P., & van Gool, W. A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0055-1 · Cited by 181 · see citing works
Insulin-Mediated Regulation of Neuronal Maturation
Puro, D. G., & Agardh, E. (1984) · Science · doi:10.1126/science.6089343 · Cited by 181 · see citing works
Mill, J. F., Chao, M. V., & Ishii, D. N. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.20.7126 · Cited by 177 · see citing works
Hoyer, S. (2004) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8969-7_8 · Cited by 173 · see citing works
Amyloid Fibril Toxicity in Alzheimer's Disease and Diabetes a
Lorenzo, A., & Yankner, B. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34406.x · Cited by 162 · see citing works
Huo, H., Guo, X., Hong, S., Jiang, M., Liu, X., & Liao, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211785200 · Cited by 145 · see citing works
Changes in Blood Glucose and Insulin Secretion in Patients with Senile Dementia of Alzheimer Type
Bucht, G., Adolfsson, R., Lithner, F., & Winblad, B. G. (1983) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1983.tb03756.x · Cited by 140 · see citing works
de la Monte, S. M., & Wands, J. R. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8475-x · Cited by 123 · see citing works
Chen, G., Xu, X. J., Lahousse, S. A., Caggiano, N. L., & de la Monte, S. M. (2003) · Journal of Alzheimer s Disease · doi:10.3233/jad-2003-5305 · Cited by 115 · see citing works
de la Monte, S. M., Ghanbari, K., Frey, W. H., Beheshti, I., Averback, P., Hauser, S. L., Ghanbari, H. A., & Wands, J. R. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119864 · Cited by 113 · see citing works
Potential Role of Pten Phosphatase in Ethanol–Impaired Survival Signaling in the Liver
Yeon, J. E., Califano, S., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2003) · Hepatology · doi:10.1053/jhep.2003.50368 · Cited by 108 · see citing works
de la Monte, S. M., Ganju, N., Banerjee, K., Brown, N. V., Luong, T., & Wands, J. R. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02044.x · Cited by 97 · see citing works
PC12 Cells Have Caveolae That Contain TrkA
Peiró, S., Comella, J. X., Enrich, C., Martı́n-Zanca, D., & Rocamora, N. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000487200 · Cited by 93 · see citing works
Diabetes, Alzheimer's disease and apolipoprotein genotype
Messier, C. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00153-0 · Cited by 92 · see citing works
Inhibition of the Neuronal Insulin Receptor An in Vivo Model for Sporadic Alzheimer Disease?
Hoyer, S., Lee, S. K., Löffler, T., & Schliebs, R. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06932.x · Cited by 87 · see citing works
Hoyer, S., & Lannert, H. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07842.x · Cited by 87 · see citing works
Tsukamoto, E., Hashimoto, Y., Kanekura, K., Niikura, T., Aiso, S., & Nishimoto, I. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10703 · Cited by 86 · see citing works
Death and survival of neuronal cells exposed to Alzheimer's insults
Niikura, T., Hashimoto, Y., Tajima, H., & Nishimoto, I. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10354 · Cited by 76 · see citing works
Ethanol impairs insulin-stimulated mitochondrial function in cerebellar granule neurons
de la Monte, S. M., Neely, T. R., Cannon, J., & Wands, J. R. (2001) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000829 · Cited by 70 · see citing works
Polymorphisms of insulin degrading enzyme gene are not associated with Alzheimer's disease
Boussaha, M., Hannequin, D., Verpillat, P., Brice, A., Frébourg, T., & Campion, D. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00586-4 · Cited by 68 · see citing works
Cho, C., Lee, C. S., Chang, M. V., Jang, I. H., Kim, S. J., Hwang, I., Ryu, S. H., Lee, C. O., & Koh, G. Y. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00786.2003 · Cited by 62 · see citing works
Hu, J., Fu, S., Zhang, K., Li, Y., Yin, L., Lu, P., & Xu, X. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20317 · Cited by 56 · see citing works
Nagy, Z., Yilmazer-Hanke, D. M., Braak, H., Braak, E., Schultz, C., & Hanke, J. (1998) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017038 · Cited by 51 · see citing works
Quantitative evaluation of the rRNA in Alzheimer's disease.
da Silva, A. M. Á., Payão, S., Borsatto, B., Bertolucci, P., & Smith, M. D. A. C. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00180-9 · Cited by 46 · see citing works
de la Monte, S. M., Chen, G., Rivera, E. J., & Wands, J. R. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3305-3 · Cited by 44 · see citing works
Ribosomal RNA in Alzheimer's disease and ageing
Payão, S., Smith, M. D. A. C., Winter, L. M. F., & Bertolucci, P. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00095-5 · Cited by 42 · see citing works
de la Monte, S. M., & Wands, J. R. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.2.195 · Cited by 38 · see citing works
de la Monte, S. M., & Wands, J. R. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6304 · Cited by 31 · see citing works
Intrinsic kinase activity of the insulin receptor
O'Hare, T., & Pilch, P. F. (1990) · International Journal of Biochemistry · doi:10.1016/0020-711x(90)90132-m · Cited by 29 · see citing works
Somatostatin: alterations in the central nervous system in neurological diseases.
Beal, M. F., Uhl, G. R., Mazurek, M. F., Kowall, N. W., & Martin, J. B. (1986) · PubMed · Cited by 28 · see citing works
Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2
Meuillet, E. J., Leray, V., Hubert, P., Leray, C., & Crémel, G. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(99)00023-x · Cited by 26 · see citing works
Metabolic Changes in Alzheimer's Disease
Fisman, M., Gordon, B. A., Feleki, V., Helmes, E., McDonald, T. J., & Dupre, J. (1988) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1988.tb02354.x · Cited by 25 · see citing works
Diabetes Mellitus with Mitochondrial Gene Mutations in Japan
Suzuki, S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.019 · Cited by 23 · see citing works
Microtiter Immunocytochemical ELISA Assay
de la Monte, S. M., Ganju, N., & Wands, J. R. (1999) · BioTechniques · doi:10.2144/99266bm15 · Cited by 22 · see citing works
Somatostatin and Alzheimer's disease: a hypothesis
Reubi, J. C., & Palacios, J. M. (1986) · Journal of Neurology · doi:10.1007/bf00313925 · Cited by 17 · see citing works
Tham, A., Björkstén, K. S., Bowen, D. M., Wetterberg, L., & Sara, V. R. (1988) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1988.tb05193.x · Cited by 13 · see citing works
Kumagai, T., Kitagawa, Y., Hirose, G., & Sakai, K. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00184-2 · Cited by 10 · see citing works
Somatostatin and Alzheimer's disease
Hoyer, S. (1987) · Journal of Neurology · doi:10.1007/bf00618265 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871 · see citing works
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Alzheimer’s disease is type 3 diabetes—Evidence reviewed
de la Monte, S. M., & Wands, J. R. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200619 · Cited by 1,158 · see citing works
Trends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939 · see citing works
Chen, Z., & Zhong, C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.004 · Cited by 671 · see citing works
Is Alzheimer’s disease a type 3 diabetes? A critical appraisal
Kandimalla, R., Thirumala, V., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.08.018 · Cited by 621 · see citing works
Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans
Kullmann, S., Heni, M., Hallschmid, M., Fritsche, A., Preissl, H. T., & Häring, H. (2016) · Physiological Reviews · doi:10.1152/physrev.00032.2015 · Cited by 632 · see citing works
Hopperton, K. E., Mohammad, D., Trépanier, M. O., Giuliano, V, & Bazinet, R. P. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.246 · Cited by 567 · see citing works
Ma, Q.-L., Yang, F., Rosario, E. R., Ubeda, O. J., Beech, W., Gant, D. J., Chen, P. P., Hudspeth, B., Chen, C., Zhao, Y., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1071-09.2009 · Cited by 536 · see citing works
Mechanisms of Vascular Aging: New Perspectives
Ungvari, Z. I., Kaley, G., de Cabo, R., Sonntag, W. E., & Csiszár, A. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq113 · Cited by 534 · see citing works
Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Mehran, A. E., Templeman, N. M., Brigidi, G. S., Lim, G. E., Chu, K.-Y., Hu, X., Botezelli, J. D., Asadi, A., Hoffman, B. G., Kieffer, T. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.019 · Cited by 498 · see citing works
Verdile, G., Keane, K. N., Cruzat, V. F., Medic, S., Sabale, M., Rowles, J., Wijesekara, N., Martins, R. N., Fraser, P. E., & Newsholme, P. (2015) · Mediators of Inflammation · doi:10.1155/2015/105828 · Cited by 501 · see citing works
Intracerebral streptozotocin model of type 3 diabetes: Relevance to sporadic Alzheimer’s disease
Lester-Coll, N., Rivera, E. J., Soscia, S. J., Doiron, K., Wands, J. R., & de la Monte, S. M. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9102 · Cited by 467 · see citing works
Freiherr, J., Hallschmid, M., Frey, W. H., Brünner, Y. F., Chapman, C. D., Hölscher, C., Craft, S., Felice, F. G. D., & Benedict, C. (2013) · CNS Drugs · doi:10.1007/s40263-013-0076-8 · Cited by 470 · see citing works
Claxton, A., Baker, L. D., Hanson, A., Trittschuh, E. H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., & Craft, S. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-141791 · Cited by 467 · see citing works
Brain metabolic dysfunction at the core of Alzheimer's disease
de la Monte, S. M., & Tong, M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.012 · Cited by 462 · see citing works
Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimers Disease
de la Monte, S. M. (2012) · Current Alzheimer Research · doi:10.2174/156720512799015037 · Cited by 446 · see citing works
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442 · see citing works
Mitochondria and Cardiovascular Aging
Dai, D., Rabinovitch, P. S., & Ungvari, Z. I. (2012) · Circulation Research · doi:10.1161/circresaha.111.246140 · Cited by 435 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Butterfield, D. A., Di Domenico, F., & Barone, E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.010 · Cited by 402 · see citing works
Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway
Gabbouj, S., Ryhänen, S., Marttinen, M., Wittrahm, R., Takalo, M., Kemppainen, S., Martiskainen, H., Tanila, H., Haapasalo, A., Hiltunen, M., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00629 · Cited by 401 · see citing works
Insulin resistance and Alzheimer's disease
De La Monte, S. M. (2009) · BMB Reports · doi:10.5483/bmbrep.2009.42.8.475 · Cited by 392 · see citing works
(Pre)diabetes, brain aging, and cognition
Roriz‐Filho, J. S., Roriz, T. M. D. S., Rosset, I., Camozzato, A. L., dos Santos, A. C., Chaves, M. L. F., Moriguti, J. C., & Roriz‐Cruz, M. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.12.003 · Cited by 390 · see citing works
Diabetes mellitus and Alzheimer's disease: shared pathology and treatment?
Akter, K., Lanza, E. A., Martin, S. A., Myronyuk, N., Rua, M., & Raffa, R. B. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2010.03830.x · Cited by 352 · see citing works
Metabolic-cognitive syndrome: A cross-talk between metabolic syndrome and Alzheimer's disease
Frisardi, V., Solfrizzi, V., Seripa, D., Capurso, C. A., Santamato, A., Sancarlo, D., Vendemiale, G., Pilotto, A., & Panza, F. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.04.007 · Cited by 357 · see citing works
Oral inflammation and infection, and chronic medical diseases: implications for the elderly
Scannapieco, F. A., & Cantos, A. (2016) · Periodontology 2000 · doi:10.1111/prd.12129 · Cited by 361 · see citing works
Jeon, B. T., Jeong, E. A., Shin, H. J., Lee, Y., Lee, D. H., Kim, H. J., Kang, S. S., Cho, G. J., Choi, W. S., & Roh, G. S. (2012) · Diabetes · doi:10.2337/db11-1498 · Cited by 352 · see citing works
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604681103 · Cited by 388 · see citing works
Michailidis, M., Moraitou, D., Tata, D. A., Kalinderi, K., Papamitsou, T., & Papaliagkas, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052687 · Cited by 330 · see citing works
de la Monte, S. M. (2017) · Drugs · doi:10.1007/s40265-016-0674-0 · Cited by 331 · see citing works
de la Monte, S. M., Tong, M., Lester-Coll, N. H., Plater, M. E., & Wands, J. R. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-10113 · Cited by 324 · see citing works
Insulin in Central Nervous System: More than Just a Peripheral Hormone
Duarte, A. I., Moreira, P. I., & Oliveira, C. R. (2012) · Journal of Aging Research · doi:10.1155/2012/384017 · Cited by 324 · see citing works
de la Monte, S. M., & Wands, J. R. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9209 · Cited by 318 · see citing works
Type 3 diabetes is sporadic Alzheimer׳s disease: Mini-review
de la Monte, S. M. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.06.008 · Cited by 312 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
The Therapeutic Potential of Metformin in Neurodegenerative Diseases
Rotermund, C., Machetanz, G., & Fitzgerald, J. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00400 · Cited by 310 · see citing works
Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives
Béard, E., Lengacher, S., Dias, S., Magistretti, P. J., & Finsterwald, C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2021.825816 · Cited by 309 · see citing works
The Mechanisms of Action of Curcumin in Alzheimer’s Disease
Tang, M., & Taghibiglou, C. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170188 · Cited by 311 · see citing works
Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart
Benedict, C., Hallschmid, M., Schmitz, K., Schultes, B., Ratter, F., Fehm, H. L., Born, J., & Kern, W. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301193 · Cited by 302 · see citing works
Gupta, A., Bisht, B., & Dey, C. S. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.033 · Cited by 302 · see citing works
Aging and Alzheimer's disease: comparison and associations from molecular to system level
Xia, X., Jiang, Q., McDermott, J., & Han, J. J. (2018) · Aging Cell · doi:10.1111/acel.12802 · Cited by 301 · see citing works
Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment
Li, X., Leng, S. X., & Song, D. (2015) · Clinical Interventions in Aging · doi:10.2147/cia.s74042 · Cited by 294 · see citing works
Aberrant insulin signaling in Alzheimer's disease: current knowledge
Bedse, G., Domenico, F. D., Serviddio, G., & Cassano, T. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00204 · Cited by 294 · see citing works
The role of type 2 diabetes in neurodegeneration
Verdile, G., Fuller, S. J., & Martins, R. N. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.04.008 · Cited by 276 · see citing works
de la Monte, S. M. (2012) · Drugs · doi:10.2165/11597760-000000000-00000 · Cited by 265 · see citing works
Diabetes mellitus and cognitive impairments
Saedi, E., Gheini, M. R., Faiz, F., & Arami, M. A. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i17.412 · Cited by 269 · see citing works
Insulin Resistance and Oxidative Stress in the Brain: What’s New?
Maciejczyk, M., Żebrowska, E., & Chabowski, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040874 · Cited by 262 · see citing works
Diabetes and Alzheimer’s disease crosstalk
Baglietto‐Vargas, D., Shi, J. J., Yaeger, D. M., Ager, R. R., & LaFerla, F. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.005 · Cited by 254 · see citing works
The relationship between Alzheimer's disease and diabetes: Type 3 diabetes?
Kroner, Z. (2009) · PubMed · Cited by 246 · see citing works
Mechanisms Underlying Caloric Restriction and Lifespan Regulation
Ungvari, Z. I., Parrado‐Fernández, C., Csiszár, A., & de Cabo, R. (2008) · Circulation Research · doi:10.1161/circresaha.107.168369 · Cited by 239 · see citing works
Insulin Dysfunction InducesIn VivoTau Hyperphosphorylation through Distinct Mechanisms
Planel, E., Tatebayashi, Y., Miyasaka, T., Liu, L., Wang, L., Herman, M., Yu, W. H., Luchsinger, J. A., Wadzinski, B. E., Duff, K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3949-07.2007 · Cited by 238 · see citing works
Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease
Atamna, H., & Frey, W. H. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.06.001 · Cited by 278 · see citing works
McNay, E. C., & Recknagel, A. K. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.005 · Cited by 229 · see citing works
Insulin, cognition, and dementia
Cholerton, B., Baker, L. D., & Craft, S. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.08.008 · Cited by 229 · see citing works
Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease
Burillo, J., Marqués, P., Jiménez, B., González-Blanco, C., Benito, M., & Guillén, C. (2021) · Cells · doi:10.3390/cells10051236 · Cited by 234 · see citing works
Lee, C.-C., Huang, C., & Hsu, K. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.06.003 · Cited by 227 · see citing works
Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy
Westwood, A. J., Beiser, A., DeCarli, C. S., Harris, T. B., Chen, T. C., He, X., Roubenoff, R., Pikula, A., Au, R., Braverman, L. E., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000382 · Cited by 224 · see citing works
AMP‐activated protein kinase: a potential player in Alzheimer’s disease
Salminen, A., Kaarniranta, K., Haapasalo, A., Soininen, H. S., & Hiltunen, M. O. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07331.x · Cited by 221 · see citing works
Freude, S., Hettich, M. M., Schumann, C., Stöhr, O., Koch, L., Köhler, C., Udelhoven, M., Leeser, U., Müller, M., Kubota, N., et al. (2009) · The FASEB Journal · doi:10.1096/fj.09-132043 · Cited by 218 · see citing works
Claxton, A., Baker, L. D., Wilkinson, C. W., Trittschuh, E. H., Chapman, D., Watson, G. S., Cholerton, B., Plymate, S. R., Arbuckle, M., & Craft, S. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-122308 · Cited by 215 · see citing works
Insulin-resistant brain state: The culprit in sporadic Alzheimer's disease?
Correia, S. C., Santos, R. X., Perry, G., Zhu, X., Moreira, P. I., & Smith, M. A. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.01.001 · Cited by 212 · see citing works
Neuronal Apoptosis in Neurodegeneration
Okouchi, M., Ekshyyan, O. Y., Maracine, M., & Aw, T. Y. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1511 · Cited by 219 · see citing works
Modifiable Risk Factors for Alzheimer’s Disease
Edwards III, G. A., Gamez, N., Escobedo Jr., G., Calderon, O., & Moreno-Gonzalez, I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00146 · Cited by 253 · see citing works
Yarchoan, M. M., Toledo, J. B., Lee, E. B., Arvanitakis, Z., Kazi, H., Han, L.-Y., Louneva, N., Lee, V. M. ‐., Kim, S. F., Trojanowski, J. Q., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1328-5 · Cited by 206 · see citing works
Hewston, P. A., & Deshpande, N. (2016) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2015.08.005 · Cited by 205 · see citing works
Bharadwaj, P., Wijesekara, N., Liyanapathirana, M., Newsholme, P., Ittner, L. M., Fraser, P. E., & Verdile, G. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161192 · Cited by 203 · see citing works
Molecular links between Alzheimer’s disease and diabetes mellitus
Yang, Y., & Song, W. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.009 · Cited by 201 · see citing works
The Aging Heart: Figure 1.Preprint
Chiao, Y. A., & Rabinovitch, P. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025148 · Cited by 198 · see citing works
Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?
Stanley, M., Macauley, S. L., & Holtzman, D. M. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160493 · Cited by 199 · see citing works
Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond Memory Defects
Frozza, R. L., Lourenco, M. V., & Felice, F. G. D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00037 · Cited by 202 · see citing works
Correia, S. C., Santos, R. X., Carvalho, C., Cardoso, S., Candeias, E., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2012) · Brain Research · doi:10.1016/j.brainres.2011.12.063 · Cited by 195 · see citing works
Rojas-Gutierrez, E., Muñoz‐Arenas, G., Treviño, S., Espinosa, B., Chávez, R., Rojas, K., Flores, G., Díaz, A., & Guevara, J. (2017) · Synapse · doi:10.1002/syn.21990 · Cited by 193 · see citing works
Ke, Y. D., Delerue, F., Gladbach, A., Götz, J., & Ittner, L. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007917 · Cited by 189 · see citing works
Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes
Moreira, P. I., Santos, M. S., Seiça, R. M. F., & Oliveira, C. R. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.017 · Cited by 190 · see citing works
The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer’s Disease
Cole, G. M., & Frautschy, S. A. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.08.009 · Cited by 189 · see citing works
Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support
Marsh, S. E., & Blurton-Jones, M. M. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.006 · Cited by 182 · see citing works
Clinical development of curcumin in neurodegenerative disease
Hu, S., Maiti, P., Ma, Q., Zuo, X., Jones, M. R., Cole, G. M., & Frautschy, S. A. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1044981 · Cited by 179 · see citing works
Type 2 diabetes as a risk factor for cognitive impairment: current insights
Umegaki, H. (2014) · Clinical Interventions in Aging · doi:10.2147/cia.s48926 · Cited by 180 · see citing works
Impaired insulin signalling and allostatic load in Alzheimer disease
Felice, F. G. D., Gonçalves, R. A., & Ferreira, S. T. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00558-9 · Cited by 180 · see citing works
Intranasal Insulin for Alzheimer’s Disease
Hallschmid, M. (2021) · CNS Drugs · doi:10.1007/s40263-020-00781-x · Cited by 182 · see citing works
Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline
Ehtewish, H., Arredouani, A., & El‐Agnaf, O. M. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116144 · Cited by 184 · see citing works
Barone, E., Domenico, F. D., Perluigi, M., & Butterfield, D. (2021) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2021.09.006 · Cited by 155 · see citing works
de la Monte, S. M., Longato, L., Tong, M., & Wands, J. R. (2009) · PubMed · Cited by 167 · see citing works
Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine
Eid, A., Mhatre, I., & Richardson, J. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.03.005 · Cited by 164 · see citing works
Insulin resistance and pathological brain ageing
Cholerton, B., Baker, L. D., & Craft, S. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03464.x · Cited by 160 · see citing works
Werner, H., & LeRoith, D. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.020 · Cited by 159 · see citing works
Wang, X., Zheng, W. H., Xie, J., Wang, T., Wang, S., Teng, W., & Wang, Z. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-46 · Cited by 161 · see citing works
Metabolic syndrome and the role of dietary lifestyles in Alzheimer’s disease
Pasinetti, G. M., & Eberstein, J. A. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05454.x · Cited by 157 · see citing works
Insulin and Alzheimer's Disease: Untangling the Web
Craft, S., Cholerton, B., & Baker, L. D. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129042 · Cited by 157 · see citing works
Shared links between type 2 diabetes mellitus and Alzheimer's disease: A review
Mittal, K., & Katare, D. P. (2016) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2016.01.021 · Cited by 154 · see citing works
Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment
Bayer-Carter, J. L., Green, P. S., Montine, T. J., VanFossen, B. T., Baker, L. D., Watson, G. S., Bonner, L. M., Callaghan, M., Leverenz, J. B., Walter, B. K., et al. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.125 · Cited by 154 · see citing works
Devi, L., Alldred, M. J., Ginsberg, S. D., & Ohno, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032792 · Cited by 155 · see citing works
Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus
Moroz, N., Tong, M., Longato, L., Xu, H., & de la Monte, S. M. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15103 · Cited by 151 · see citing works
Sanders, L. M. J., Hortobágyi, T., Karssemeijer, E. G. A., Van der Zee, E. A., Scherder, E. J. A., & van Heuvelen, M. J. G. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00597-3 · Cited by 154 · see citing works
Lyn‐Cook, L. E., Lawton, M., Tong, M., Silbermann, E., Longato, L., Jiao, P., Mark, P., Wands, J. R., Xu, H., & de la Monte, S. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0984 · Cited by 149 · see citing works
Insulin‐like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice
Pascual‐Lucas, M., da Silva, S. V., Scala, M. D., García, C., González‐Aseguinolaza, G., Mulle, C., Alberini, C. M., Cuadrado‐Tejedor, M., & García‐Osta, A. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404228 · Cited by 147 · see citing works
Metabolic Syndrome as a Risk Factor for Alzheimer’s Disease: A Focus on Insulin Resistance
Ezkurdia, A., Ramírez, M. J., & Solas, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054354 · Cited by 153 · see citing works
- Authors
- Rivera, E. J., Goldin, A., Fulmer, N., Tavares, R., Wands, J. R., & de la Monte, S. M.
- Affiliations
- Brown University (US)
- Departments of Pathology and Medicine, Rhode Island Hospital and Brown Medical School, Providence, RI, USA
- ORCID
- Wands, Jack R.
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2005-12-05
- Volume
- 8
- Issue
- 3
- Pages
- 247-268
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1718410121
- Cited by
- 723
- References
- 71
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 32 · 2023: 35 · 2022: 56 · 2021: 45 · 2020: 43 · 2019: 52 · 2018: 46 · 2017: 29 · 2016: 43 · 2015: 44 · 2014: 51 · 2013: 42 · 2012: 43
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA12458, AA-02666, AA11931)
- National Institute on Aging (P50 AG05128, P50AG005128)
- National Center for Research Resources (P20RR 15578, P20RR015578)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, insulin
- MeSH terms
- Acetylcholine, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Brain, Choline O-Acetyltransferase, Cognition Disorders, Female, Genotype, Glucose, Humans, Insulin, Insulin Resistance, Insulin-Like Growth Factor I, Male, RNA, Messenger, Gene Expression, Amyloid beta-Protein Precursor, tau Proteins, DNA Primers, Disease Progression, Reverse Transcriptase Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
