Cited by 723Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.

Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: Link to brain reductions in acetylcholine

Rivera, Enrique J., Goldin, Alison, Fulmer, Noah, Tavares, Rose, Wands, Jack R., de la Monte, Suzanne M.·2005·Journal of Alzheimer s Disease

DOI 10.3233/jad-2005-8304

Open this paper in CoChat — free account

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

Crossref · 10.3233/jad-2005-8304

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

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
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
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 2,076
Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes?
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
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
Editorial on Consensus Recommendations for the Postmortem Diagnosis of Alzheimer Disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer Disease
HYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542
Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J. R., & Dedhar, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11211 · Cited by 1,102
Antiapoptotic Signalling by the Insulin-Like Growth Factor I Receptor, Phosphatidylinositol 3-Kinase, and Akt
Kulik, G., Klippel, A., & Weber, M. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1595 · Cited by 1,038
A Novel Geneiba1in the Major Histocompatibility Complex Class III Region Encoding an EF Hand Protein Expressed in a Monocytic Lineage
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 · cited 1×
“Signiﬁcant P-values are indicated over the bar graphs. and ionized calcium-binding adaptor molecule 1 (IBA-1) to speciﬁcally detect neurons (Hu) [31–33], astrocytes (GFAP), or microglial cells (AIF1 and IBAI) [34, 35] (Table 2).”
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

Flagged first, then by citations

Show all 71 references

Sorted by citations

Items 101–200 of 721

Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-β Clearance
Gontier, G., George, C., Chaker, Z., Holzenberger, M., & Aïd, S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0343-15.2015 · Cited by 145
“Abnormalities in IGF-1R expression and activation, including IGF-I resistance, exist in AD brains (Rivera et al., 2005; Steen et al., 2005; Moloney et al., 2010; Bomfim et al., 2012; Talbot et al., 2012), although causality is not clear.”
Background
Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain
Liu, C., Hu, J., Tsai, C., Yue, M., Melrose, H. L., Kanekiyo, T., & Bu, G. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5180-14.2015 · Cited by 145
“, 2005) and reduced activation of the receptor tyrosine kinase domain in AD brains (Rivera et al., 2005; Talbot et al., 2012).”
Background
Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity
Chan, K., Lam, K. S. L., Cheng, O.-Y., Kwan, J., Ho, P. W., Cheng, K. K. Y., Chung, S. K., Ho, J. W.-M., Guo, V. Y., & Xu, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052354 · Cited by 143
“Insulin is important for neuronal function and survival, and reduced cerebral insulin and insulin-like growth factor (IGF-1) levels, as well as impaired neuronal insulin signaling are noted in AD brain [63–64].”
Background
Brain Insulin Resistance in Alzheimer's Disease and its Potential Treatment with GLP-1 Analogs
Talbot, K. (2014) · Neurodegenerative Disease Management · doi:10.2217/nmt.13.73 · Cited by 141
The nature, significance, and glucagon‐like peptide‐1 analog treatment of brain insulin resistance in Alzheimer's disease
Talbot, K., & Wang, H.-Y. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.007 · Cited by 142
“Among the most often cited causes are: (a) reduced extracellular insulin deduced from CSF assays [60,61]; (b) reduced total [37] or cell surface [40,72] IR expression; and (c) reduced IR affinity for insulin [17].”
BackgroundInfluential
Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review
Berlanga‐Acosta, J., Guillén, G. E., Rodríguez-Rodríguez, N., Bringas-Vega, M. L., García-del-Barco-Herrera, D., Berlanga-Saez, J. O., Ojalvo, A. G., Valdés-Sosa, M. J., & Valdes-Sosa, P. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.560375 · Cited by 143
Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity
Garinis, G. A., Uittenboogaard, L. M., Stachelscheid, H., Fousteri, M., van Ijcken, W., Breit, T. M., van Steeg, H., Mullenders, L. H. F., van der Horst, G. T. J., Brüning, J. C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1866 · Cited by 138
Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloidpeptide, insulin signaling, and neuronal function
Takeda, S., Sato, N., Rakugi, H., & Morishita, R. (2011) · Molecular BioSystems · doi:10.1039/c0mb00302f · Cited by 141
Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer’s disease
Ceccom, J., Loukh, N., Lauwers‐Cancès, V., Touriol, C., Nicaise, Y., Gentil, C., Uro‐Coste, E., Pitson, S. M., Maurage, C., Duyckaerts, C. J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-12 · Cited by 140
“This result is consistent with literature [23] and introduces a possible candidate for mediating signaling between Aβ and SphK1.”
BackgroundResult
Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition
Adler, B. L., Yarchoan, M. M., Hwang, H. M., Louneva, N., Blair, J. A., Palm, R. F., Smith, M. A., Lee, H., Arnold, S. E., & Casadesús, G. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.10.076 · Cited by 132
“Moreover, neuropathologic studies demonstrate altered insulin signaling in AD brains consistent with insulin resistance (De la Monte and Wands, 2008; Rivera et al., 2005; Steen et al., 2005).”
Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition
Salameh, T. S., Bullock, K. M., Hujoel, I. A., Niehoff, M. L., Wolden‐Hanson, T., Kim, J., Morley, J. E., Farr, S. A., & Banks, W. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150307 · Cited by 136
“In support of this hypothesis, studies have demonstrated that patients with AD have reduced brain insulin receptor sensitivity [3, 4], hypophosphorylation of the insulin receptor and downstream second messengers such as insulin receptor substrate-1 [4, 5], and attenuated insulin and insulin-like growth factor receptor…”
Result
Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment
Chakrabarti, S., Kumar Khemka, V., Banerjee, A., Chatterjee, G., Ganguly, A., & Biswas, A. (2015) · Aging and disease · doi:10.14336/ad.2014.002 · Cited by 134
Brain Metabolic Alterations in Alzheimer’s Disease
Ardanaz, C. G., Ramírez, M. J., & Solas, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073785 · Cited by 135
Update on Vascular Cognitive Impairment Associated with Subcortical Small-Vessel Disease
Wallin, A., Román, G. C., Esiri, M. M., Kettunen, P., Svensson, J., Paraskevas, G. P., & Kapaki, E. N. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170803 · Cited by 133
Insulin resistance in Alzheimer's disease
Dineley, K. T., Jahrling, J. B., & Denner, L. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.09.001 · Cited by 125
Modeling Sporadic Alzheimer's Disease: The Insulin Resistant Brain State Generates Multiple Long-Term Morphobiological Abnormalities Including Hyperphosphorylated Tau Protein and Amyloid-β
Šalković‐Petrišić, M., Barilar, J. O., Grünblatt, E., Riederer, P. F., & Hoyer, S. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1184 · Cited by 122
“In contrast, in the anterior frontal cortex, AβPP mRNA was low in the normal brain but increased with advancing dementia, whereas tau mRNA showed an inverse pattern [175].”
BackgroundInfluential
Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease
Camandola, S., & Mattson, M. P. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.10.005 · Cited by 128
Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice
Meakin, P. J., Harper, A. J., Hamilton, D. L., Gallagher, J., McNeilly, A. D., Burgess, L. A., Vaanholt, L. M., Bannon, K. A., Latcham, J., Hussain, I., et al. (2012) · Biochemical Journal · doi:10.1042/bj20110512 · Cited by 103
The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114
“AD patients show reduced brain IR sensitivity (214, 250), hypophosphorylation of the IR, and downstream second messengers such as IRS-1 (233, 250) and attenuated insulin and IGF-1R expression (233).”
Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms
Wei, Z.-H., Koya, J., & Reznik, S. E. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.687157 · Cited by 133
Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease
Bohnen, N. I., Kotagal, V., Müller, M. L. T. M., Koeppe, R. A., Scott, P. J. H., Albin, R. L., Frey, K. A., & Petrou, M. (2014) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2014.10.008 · Cited by 114
“Impaired glucose metabolism may lead to cholinergic system dysfunction (30, 31).”
Background
Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction
Stoeckel, L. E., Arvanitakis, Z., Gandy, S., Small, D. M., Kahn, C. R., Pascual‐Leone, Á., Pawlyk, A. C., Sherwin, R., & Smith, P. (2016) · F1000Research · doi:10.12688/f1000research.8300.2 · Cited by 113
Cerebrovascular insulin receptors are defective in Alzheimer’s disease
Leclerc, M., Bourassa, P., Tremblay, C., Caron, V., Sugère, C., Émond, V., Bennett, D. A., & Calon, F. (2022) · Brain · doi:10.1093/brain/awac309 · Cited by 113
Effects of Meditation versus Music Listening on Perceived Stress, Mood, Sleep, and Quality of Life in Adults with Early Memory Loss: A Pilot Randomized Controlled Trial
Innes, K. E., Selfe, T. K., Khalsa, D. S., & Kandati, S. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151106 · Cited by 114
“Likewise, recent research in healthy adults [169–171], lonely older adults [172], and depressed dementia caregivers [173, 174] suggest that meditation may also buffer or reverse multiple stress-related changes in specific gene expression pathways implicated in the development and progression of AD, including those reg…”
Role of Gut Microbiota in Obesity, Type 2 Diabetes and Alzheimer’s Disease
Naseer, M. I., Bibi, F., Al-Qahtani, M. H., Chaudhary, A., Azhar, E. I., Kamal, M. A., & Yasir, M. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113126660147 · Cited by 109
“Further the roles of T2DM, peripheral insulin resistance, and hyperinsulinemia in relation to cognitive impairment and its progression to AD exploding with new information about the mechanisms of brain insulin resistance, cognitive impairment and neurodegeneration [83-90].”
Background
Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease
Amato, A., Terzo, S., & Mulè, F. (2019) · Antioxidants · doi:10.3390/antiox8120608 · Cited by 107
“Accordingly, obesity-related brain-specific insulin resistance, known as type III diabetes [40,41], has been reported in dementia, including AD, suggesting that it may contribute to neurodegeneration [42,43].”
Background
Mitochondria and aging in the vascular system
Ungvari, Z., Sonntag, W. E., & Csiszar, A. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0667-5 · Cited by 103
“The available data support the conclusion that supplementation of IGF-1 may exert vasculoprotective effects in aging [20, 21], improving cardiac diastolic function [22], and preventing hippocampal microvascular rarefaction [8, 23, 24].”
Effect of Apolipoprotein E Genotype and Diet on Apolipoprotein E Lipidation and Amyloid Peptides
Hanson, A. J., Bayer-Carter, J. L., Green, P. S., Montine, T. J., Wilkinson, C. W., Baker, L. D., Watson, G. S., Bonner, L. M., Callaghan, M., Leverenz, J. B., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.396 · Cited by 110
Triangulated Mal-Signaling in Alzheimer's Disease: Roles of Neurotoxic Ceramides, ER Stress, and Insulin Resistance Reviewed
de la Monte, S. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111727 · Cited by 104
Insulin and Insulin‐Like Growth Factor Resistance With Neurodegeneration in an Adult Chronic Ethanol Exposure Model
Cohen, A. C., Tong, M., Wands, J. R., & de la Monte, S. M. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00450.x · Cited by 102
Down Syndrome Is a Metabolic Disease: Altered Insulin Signaling Mediates Peripheral and Brain Dysfunctions
Dierssen, M., Fructuoso, M., de Lagrán, M. M., Marzia Perluigi, A., & Barone, E. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00670 · Cited by 106
Impairment of biliverdin reductase-A promotes brain insulin resistance in Alzheimer disease: A new paradigm
Barone, E., Di Domenico, F., Cassano, T., Arena, A., Tramutola, A., Lavecchia, M. A., Coccia, R., Butterfield, D. A., & Perluigi, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.012 · Cited by 100
Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation, hyperphosphorylation of tau and behavioral deficits in mice
Yang, Z., Gu, J., Dai, C., Liu, Q., Iqbal, K., Liu, F., & Gong, C. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00010 · Cited by 100
Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain
Soscia, S. J., Tong, M., Xu, X. J., Cohen, A. C., Chu, J., Wands, J. R., & de la Monte, S. M. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6208-2 · Cited by 100
G-protein coupled receptor, PI3K and Rho signaling pathways regulate the cascades of Tau and amyloid-β in Alzheimer’s disease
Desale, S. E., Chidambaram, H., & Chinnathambi, S. (2021) · Molecular Biomedicine · doi:10.1186/s43556-021-00036-1 · Cited by 99
“TREM2 knockdown decreases the level of AKT and GSK-3β, which indicates that TREM-2 mediated stabilization of β-catenin is via AKT/ GSK-3β signaling pathway [90, 102].”
Background
Mechanisms of Nitrosamine-Mediated Neurodegeneration: Potential Relevance to Sporadic Alzheimer's Disease
de la Monte, S. M., & Tong, M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1098 · Cited by 102
“Recent studies have linked the molecular and bio-chemical pathology of AD to impairments in insulin and IGF signaling mechanisms in the brain [14,16,44, 45].”
Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections
Schmitz, T. W., Mur, M., Aghourian, M., Bédard, M., & Spreng, R. N. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.001 · Cited by 99
“, 1995) and reduced metabolism (Rivera et al., 2005) contributing to differentiate normal age-related from AD trajectories of cholinergic loss.”
Cross-disease analysis of Alzheimer’s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases
Caberlotto, L., Nguyen, T.-P., Lauria, M., Priami, C., Rimondini, R., Maioli, S., Cedazo-Mínguez, Á., Sita, G., Morroni, F., Corsi, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-39828-5 · Cited by 99
Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats
Yang, W., Ma, J., Liu, Z., Lu, Y., Hu, B., & Yu, H. (2013) · Neurological Sciences · doi:10.1007/s10072-013-1594-3 · Cited by 99
“Recently, several experimental studies show that choline acetyltransferase gene expression is regulated by insulin [30].”
Background
Disentangling Mitochondria in Alzheimer’s Disease
Johri, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111520 · Cited by 103
Brain Insulin-Like Growth Factor and Neurotrophin Resistance in Parkinson's Disease and Dementia with Lewy Bodies: Potential Role of Manganese Neurotoxicity
Tong, M., Dong, M., & de la Monte, S. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0995 · Cited by 95
“Previous studies demonstrated signiﬁcant pathological shifts in brain cell populations that correlated with neuronal and oligodendroglial cell loss, gliosis, and neuroinﬂammation in AD [31].”
Influential
Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
Rodriguez‐Rodriguez, P., Matton, A., Merino‐Serrais, P., Parrado‐Fernández, C., Rábano, A., Winblad, B. G., Ávila, J., Ferrer, I., & Cedazo-Mínguez, Á. (2017) · Brain · doi:10.1093/brain/awx256 · Cited by 99
“, 2010) and post-mortem analysis of Alzheimer’s disease brains has shown downregulated insulin and insulin receptor mRNA levels, together with insulin and insulin receptor substrate 1 (IRS1) signalling impairments (Rivera et al., 2005; Talbot et al., 2012).”
Background
Cognitive dysfunctions in individuals with diabetes mellitus
Kim, H.-G. (2019) · Journal of Yeungnam Medical Science · doi:10.12701/yujm.2019.00255 · Cited by 100
“To consolidate this concept, numerous investigators have proposed that AD should be referred to as type 3 DM [60,61].”
Background
IGF2 Ameliorates Amyloidosis, Increases Cholinergic Marker Expression and Raises BMP9 and Neurotrophin Levels in the Hippocampus of the APPswePS1dE9 Alzheimer’s Disease Model Mice
Mellott, T. J., Pender, S. M., Burke, R. M., Langley, E. A., & Blusztajn, J. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094287 · Cited by 93
“cortex of AD patients at relatively early stages of neuropathology (Braak and Braak 2–3) [9] and on a growing body of data showing”
Background
Neurodegeneration in Diabetes Mellitus
Umegaki, H. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0653-2_19 · Cited by 94
Increased Circulating Insulin-like Growth Factor-1 in Late-onset Alzheimer's Disease
Vardy, E. R. L. C., Rice, P. J., Bowie, P. C. W., Holmes, J. D., Grant, P. J., & Hooper, N. M. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-12401 · Cited by 91
Meditation and Music Improve Memory and Cognitive Function in Adults with Subjective Cognitive Decline: A Pilot Randomized Controlled Trial
Innes, K. E., Selfe, T. K., Khalsa, D. S., & Kandati, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160867 · Cited by 99
A Systematic Review of MicroRNA Expression as Biomarker of Late-Onset Alzheimer’s Disease
Herrera-Espejo, S., Santos-Zorrozua, B., Álvarez-González, P., Lopez-Lopez, E., & Garcia-Orad, Á. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01676-9 · Cited by 81
Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease
Percy, M. E., Kruck, T. P. A., Pogue, A. I., & Lukiw, W. J. (2011) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.08.001 · Cited by 89
Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art
de la Monte, S. M. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.856877 · Cited by 89
“Further, while it is still possible that brain insulin resistance represents an adaptive or protective response to hyperinsulinemia, it is unlikely that this concept has major relevance to the CNS abnormalities in mild cognitive impairment (MCI) or AD because : i) most individuals with AD and brain insulin resistance…”
Influential
Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment
de la Monte, S. M., Tong, M., Lawton, M., & Longato, L. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-54 · Cited by 88
“These impairments in the expression of genes needed for proper insulin and IGF signaling are reminiscent of those detected in human brains with AD [34,51,67].”
Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin
Santos, T. D. O., Mazucanti, C. H., Xavier, G. F., & Torrão, A. D. S. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.06.019 · Cited by 86
Aberrant protein phosphorylation in Alzheimer disease brain disturbs pro-survival and cell death pathways
Marzia Perluigi, A., Barone, E., Domenico, F. D., & Butterfield, D. A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.07.005 · Cited by 86
Roles of vascular risk factors in the pathogenesis of dementia
Takeda, S., Rakugi, H., & Morishita, R. (2019) · Hypertension Research · doi:10.1038/s41440-019-0357-9 · Cited by 94
Insulin signalling in Alzheimer′s disease and diabetes: from epidemiology to molecular links
Ribé, E. M., & Lovestone, S. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12534 · Cited by 88
Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers
Pitt, J. E., Wilcox, K. C., Tortelli, V., Diniz, L. P., Oliveira, M. S., Dobbins, C., Yu, X., Nandamuri, S., Gomes, F. C. A., DiNunno, N., et al. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-06-0416 · Cited by 87
“…cells chronically exposed to AβOs show reduced insulin/IGF1 expression Given the association of impaired insulin/IGF1 signaling with AD dementia (Rivera et al., 2005; Bomfim et al., 2012; Craft et al., 2012; Talbot et al., 2012), we investigated whether insulin/IGF1 expression in neural cells…”
BackgroundResult
Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer’s Disease
Szablewski, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158142 · Cited by 88
“Therefore, an idea has been proposed that Alzheimer’s disease can be an “insulin-resistant state” or even a “type 3 diabetes” [99,100].”
Background
Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies
Dutta, B. J., Singh, S., Seksaria, S., Gupta, G. D., & Singh, A. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106358 · Cited by 89
Mechanisms of Ceramide-Mediated Neurodegeneration
Tong, M., & de la Monte, S. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0983 · Cited by 84
“Overexpression of the A β PP gene results in increased A β PP-A β deposition in Down syndrome [57, 58] and transgenic mouse models [59], and similarly, the higher levels of A β PP expression in AD correspond with the generally increased A β PP-A β burden in AD brains [5–7].”
Sweet but Bitter: Focus on Fructose Impact on Brain Function in Rodent Models
Spagnuolo, M. S., Iossa, S., & Cigliano, L. (2020) · Nutrients · doi:10.3390/nu13010001 · Cited by 85
Deregulation of brain insulin signaling in Alzheimer’s disease
Chen, Y., Deng, Y., Zhang, B., & Gong, C. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1408-x · Cited by 82
“in AD; they are characterized by reduced amounts of insulin in the brain([68]), reduced levels of IR-binding([69-71]), and decreased responsiveness of downstream effectors to the activation of IRs .”
Background
The paradox of neuronal insulin action and resistance in the development of aging‐associated diseases
Steculorum, S. M., Solas, M., & Brüning, J. C. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.008 · Cited by 82
“This initial finding has been confirmed and extended by other investigators, who demonstrate reduced insulin levels in the cerebrospinal fluid in patients with AD and in thosewith mild cognitive impairment [48], in addition to reduced insulin signaling in the brain of those subjects [49].”
Disturbed Cross Talk between Insulin-Like Growth Factor I and AMP-Activated Protein Kinase as a Possible Cause of Vascular Dysfunction in the Amyloid Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease
Lopez‐Lopez, C., Dietrich, M. O., Metzger, F., Loetscher, H., & Torres‐Alemán, I. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4345-06.2007 · Cited by 83
“Previous studies suggested reduced IGF/insulin function in the AD brain (Rivera et al., 2005), whereas our studies indicate that in APP/PS2 mice, brain levels of both pAMPK and IGF-IR are higher than in control mice, suggesting that IGF-IR/AMPK function may be impaired in this model of AD.”
BackgroundResult
Is Insulin Resistant Brain State a Central Feature of the Metabolic-Cognitive Syndrome?
Frisardi, V., Solfrizzi, V., Capurso, C. A., Imbimbo, B. P., Vendemiale, G., Seripa, D., Pilotto, A., & Panza, F. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100015 · Cited by 85
“In addition, inhibition of insulin/IGF-1 signaling blocks the Wnt pathway [54], which negatively regulates GSK-3β via a PI3K/Aktindependent mechanism.”
Influential
Alzheimer's Disease and Diabetes: An Integrative View of the Role of Mitochondria, Oxidative Stress, and Insulin
Moreira, P. I. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111127 · Cited by 83
“This is supported by age- and AD-related decrease in insulin mRNA and protein levels [128, 129], IR or receptor for the insulin growth factor 1 (IGF-1 R) expression [130–132] insulin receptor substrate-1 (IRS-1) and IRS-2 levels and markers of Tyr kinase activity, namely phosphatidylinositol 3-kinase (PI3-K) and extra…”
Overlapped Metabolic and Therapeutic Links between Alzheimer and Diabetes
Ahmad, W. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8352-z · Cited by 80
“AD is associated with reduced insulin and insulin mRNA as well as decrease level of insulin receptors [8].”
BackgroundInfluential
IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases
Alberini, C. M. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.03.007 · Cited by 89
Serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are increased in Alzheimer's disease
Johansson, P., Åberg, D., Johansson, J.-O., Mattsson, N., Hansson, O., Åhrén, B., Isgaard, J., Åberg, N. D., Blennow, K., Zetterberg, H., et al. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.006 · Cited by 81
“In additional studies, the brain IGF-I expression as measured using RT-PCR was decreased with an accompanying reduction in IGF-I signaling in advanced human AD (Rivera et al., 2005; Steen et al., 2005).”
Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio)
Capiotti, K. M., Moraes, D. A. D., Menezes, F. P., Kist, L. W., Bogo, M. R., & da Silva, R. S. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.033 · Cited by 81
Cellular and metabolic alterations in the hippocampus caused by insulin signalling dysfunction and its association with cognitive impairment during aging and Alzheimer's disease: studies in animal models
Calvo‐Ochoa, E., & Arias, C. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2531 · Cited by 82
“It is also known that AD further increases this insulin-deficient state [47,138].”
Background
Dysfunctional Pro-Ceramide, ER Stress, and Insulin/IGF Signaling Networks with Progression of Alzheimer's Disease
de la Monte, S. M., Re, E. B., Longato, L., & Tong, M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111728 · Cited by 81
“The significance of these responses is underscored by the constitutive up-regulation of pro-ceramide genes in the biosynthetic (CERS1, CERS2, CERS4, and SPTLC1), catabolic (SMPD1), and salvage pathways (UGCG and GM3), and the finding that expression of several pro-ceramide genes, including CERS4, SPTLC1 and SMPD1, inc…”
BackgroundMethodInfluential
Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases
Du, M., Gao, Q.-Y., Liu, C., Bai, L.-Y., Li, T. X., & Wei, F. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.838173 · Cited by 80
Insulin Levels are Decreased in the Cerebrospinal Fluid of Women with Prodomal Alzheimer's Disease
Gil-Bea, F. J., Solas, M., Solomon, A., Mugueta, C., Winblad, B. G., Kivipelto, M., Ramírez, M. J., & Cedazo-Mínguez, Á. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100795 · Cited by 81
“CNS cells [2,3].”
BackgroundInfluential
Brain Alterations and Clinical Symptoms of Dementia in Diabetes: Aβ/Tau-Dependent and Independent Mechanisms
Sato, N., & Morishita, R. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00143 · Cited by 84
“In the AD brain, the levels of insulin and IGF (113) and the responses to insulin and IGF (114) are reduced.”
BackgroundInfluential
IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation
Martín, E. D., Sánchez‐Pérez, A. M., Trejo, J. L., Martin-Aldana, J. A., Cano‐Jaimez, M., Pons, S., Umanzor, C. A., Menes, L., White, M. F., & Burks, D. J. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr216 · Cited by 80
“Memory deficits that develop during the course of Alzheimer’s disease (AD) have been linked to abnormalities in circulating insulin levels and/or defects in insulin signaling pathways (Luchsinger et al. 2004; Rivera et al. 2005; Craft 2007).”
Background
High-fat diet-induced diabetes couples to Alzheimer’s disease through inflammation-activated C/EBPβ/AEP pathway
Liu, P., Wang, Z.-H., Kang, S. S., Liu, X., Xia, Y., Chan, C.-B., & Ye, K. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01600-z · Cited by 77
“The growth factor levels are markedly decreased in the central nervous system (CNS) neurons, leading to abnormal insulin and IGF-I signaling in AD brains [11, 16].”
Background
Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model
Isik, A. T., Celik, T., Ulusoy, G., Ongoru, O., Elibol, B., Doruk, H., Bozoglu, E., Kayir, H., Mas, M. R., & Akman, S. (2009) · AGE · doi:10.1007/s11357-008-9078-8 · Cited by 76
Insulin resistance in the brain: an old-age or new-age problem?
Williamson, R., McNeilly, A., & Sutherland, C. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.05.007 · Cited by 82
“However IR expression is not trivial to quantify in postmortem tissue and there is evidence for [38,39] and against [36] this hypothesis.”
Background
CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer’s Disease
Deochand, M. T. C. (2013) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000128 · Cited by 78
“02% sodium azide and protease inhibitors [11,12].”
BackgroundMethodInfluential
Improved Brain Insulin/IGF Signaling and Reduced Neuroinflammation with T3D-959 in an Experimental Model of Sporadic Alzheimer’s Disease
de la Monte, S. M., Tong, M., Schiano, I., & Didsbury, J. R. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160656 · Cited by 79
Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimerâ€™s Disease â€“ Potential Benefits and Underlying Mechanisms
Innes, K. E., & Selfe, T. K. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00040 · Cited by 72
Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology
Orr, M. E., Salinas, A., Buffenstein, R., & Oddo, S. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.006 · Cited by 78
Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity
Costello, D. A., Claret, M., Al‐Qassab, H., Plattner, F., Irvine, E. E., Choudhury, A. I., Giese, K.-P., Withers, D. J., & Pedarzani, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031124 · Cited by 73
“normal and pathological conditions ([35–38]; but see [39]).”
Background
The 20-Year Voyage Aboard the Journal of Alzheimer's Disease: Docking at ‘Type 3 Diabetes’, Environmental/Exposure Factors, Pathogenic Mechanisms, and Potential Treatments
de la Monte, S. M., Tong, M., & Wands, J. R. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170829 · Cited by 77
“molecule expression and function in the brain [17];”
Background
The Effects of Momordica charantia on Type 2 Diabetes Mellitus and Alzheimer’s Disease
Richter, E., Geetha, T., Burnett, D. O., Broderick, T. L., & Babu, J. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054643 · Cited by 90
Insulin resistance, neuroinflammation, and Alzheimer’s disease
Najem, D., Bamji‐Mirza, M., Chang, N., Liu, Q. Y., & Zhang, W. (2014) · Reviews in the Neurosciences · doi:10.1515/revneuro-2013-0050 · Cited by 76
A Common Pathogenic Mechanism Linking Type-2 Diabetes and Alzheimer's Disease: Evidence from Animal Models
Park, S. A. (2011) · Journal of Clinical Neurology · doi:10.3988/jcn.2011.7.1.10 · Cited by 74
Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin
Kenawy, S. M., Hegazy, R. R., Hassan, A. H. M., El-Shenawy, S. M. A., Gomaa, N., Zaki, H. F., & Attia, A. S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183565 · Cited by 76
Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer’s disease
Stöhr, O., Schilbach, K., Moll, L., Hettich, M. M., Freude, S., Wunderlich, F. T., Ernst, M. B., Zemva, J., Brüning, J. C., Krone, W., et al. (2011) · AGE · doi:10.1007/s11357-011-9333-2 · Cited by 73
Brain insulin resistance triggers early onset Alzheimer disease in Down syndrome
Tramutola, A., Lanzillotta, C., Di Domenico, F., Head, E., Butterfield, D. A., Perluigi, M., & Barone, E. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104772 · Cited by 73
Mitostasis, Calcium and Free Radicals in Health, Aging and Neurodegeneration
Godoy, J. A., Ríos, J. A., Picón-Pagès, P., Herrera-Fernández, V., Swaby, B., Crepin, G., Vicente, R., Fernández‐Fernández, J. M., & Muñoz, F. J. (2021) · Biomolecules · doi:10.3390/biom11071012 · Cited by 73
“Moreover, presenilin 2 (PS2), part of the γ -secretase complex that produces A β by the cleavage at the C-terminus, has been shown to increase ER–mitochondria tethering by binding and sequestering MFN2 [123,270,271], therefore, affecting mitochondrial biogenesis.”
Background
Cognitive dysfunction: An emerging concept of a new diabetic complication in the elderly
Umegaki, H., Hayashi, T., Nomura, H., Yanagawa, M., Nonogaki, Z., Nakshima, H., & Kuzuya, M. (2012) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2012.00922.x · Cited by 75
Progression of Alzheimer’s disease, tau propagation, and its modifiable risk factors
Takeda, S. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.08.005 · Cited by 75
Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease
Raimundo, A., Ferreira, S., Martins, I. C., & Menezes, R. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00035 · Cited by 74
Relationships Between Diabetes and Cognitive Impairment
de la Monte, S. M. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.09.006 · Cited by 73
“It is noteworthy that besides the impairments in brain glucose metabolism, white matter atrophy is one of the earliest abnormalities in AD.60 Hyperinsulinemia causes progressive injury to microvessels.”
Influential
Cinnamon Counteracts the Negative Effects of a High Fat/High Fructose Diet on Behavior, Brain Insulin Signaling and Alzheimer-Associated Changes
Anderson, R. A., Qin, B., Canini, F., Poulet, L., & Roussel, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083243 · Cited by 73
“Alzheimer’s Disease (AD)-type neurodegeneration [5-8].”
Age-Dependent Changes to Sphingolipid Balance in the Human Hippocampus are Gender-Specific and May Sensitize to Neurodegeneration
Couttas, T. A., Kain, N., Tran, C., Chatterton, Z., Kwok, J. B., & Don, A. S. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-171054 · Cited by 73
“The early stages of AD are accompanied by a marked reduction in cerebral glucose utilization, potentially caused by deﬁcits of insulin receptors at synaptic membranes of the cerebral cortex and hippocampus [50], as well as reductions in insulin signaling that worsen with AD progression [51].”
Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration
Tong, M., Longato, L., & de la Monte, S. M. (2010) · BMC Endocrine Disorders · doi:10.1186/1472-6823-10-4 · Cited by 73
“In the HFD+NDEA group, both GSK-3b and pGSK-3b levels were reduced, but relative reductions were greater for pGSK-3b compared with total GSK-3b, reflecting a net relative increased in GSK3b activity, similar to the findings in AD and PD in humans [29,30,104].”
BackgroundResult
Insulin-like growth factor 2 (IGF2) protects against Huntington’s disease through the extracellular disposal of protein aggregates
García-Huerta, P., Troncoso-Escudero, P., Wu, D., Thiruvalluvan, A., Cisternas-Olmedo, M., Henríquez, D. R., Plate, L., Chaná‐Cuevas, P., Saquel, C., Thielen, P., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02183-1 · Cited by 71
“IGF2 is also modulated in various pathological context including brain injury (85), schizophrenia (86), Alzheimer ́s disease (29, 87), in addition to normal aging (29, 88).”
Background
Alcohol‐Induced Disruption of Endocrine Signaling
Ronis, M. J. J., Wands, J. R., Badger, T. M., de la Monte, S. M., Lang, C. H., & Calissendorff, J. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00436.x · Cited by 71

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
DOI: 10.3233/jad-2005-8304
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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

Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: Link to brain reductions in acetylcholine

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks