CoChat
Sign Up
Cited by 33Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchPancreatic function and diabetes

Alzheimer amyloid-β- peptide disrupts membrane localization of glucose transporter 1 in astrocytes: implications for glucose levels in brain and blood

Open access
Hendrix, Rachel D., Ou, Yang, Davis, Jakeira E., Odle, Angela K., Groves, Thomas R., Allen, Antiño R., Childs, Gwen V., Barger, Steven W.·2021·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2020.10.001PMC PMC7736209
Open this paper in CoChat — free accountOpen PDF

Abstract

Alzheimer's disease (AD) is associated with disturbances in blood glucose regulation, and type-2 diabetes elevates the risk for dementia. A role for amyloid-β peptide (Aβ) in linking these age-related conditions has been proposed, tested primarily in transgenic mouse lines that overexpress mutated amyloid precursor protein (APP). Because APP has its own impacts on glucose regulation, we examined the BRI-Aβ42 line (“Aβ42-tg”), which produces extracellular Aβ1-42 in the CNS without elevation of APP. We also looked for interactions with diet-induced obesity (DIO) resulting from a high-fat, high-sucrose (“western”) diet. Aβ42-tg mice were impaired in both spatial memory and glucose tolerance. Although DIO induced insulin resistance, Aβ1-42 accumulation did not, and the impacts of DIO and Aβ on glucose tolerance were merely additive. Aβ42-tg mice exhibited no significant differences from wild-type in insulin production, body weight, lipidemia, appetite, physical activity, respiratory quotient, an-/orexigenic factors, or inflammatory factors. These negative findings suggested that the phenotype in these mice arose from perturbation of glucose excursion in an insulin-independent tissue. To wit, cerebral cortex of Aβ42-tg mice had reduced glucose utilization, similar to human patients with AD. This was associated with insufficient trafficking of glucose transporter 1 to the plasma membrane in parenchymal brain cells, a finding also documented in human AD tissue. Together, the lower cerebral metabolic rate of glucose and diminished function of parenchymal glucose transporter 1 indicate that aberrant regulation of blood glucose in AD likely reflects a central phenomenon, resulting from the effects of Aβ on cerebral parenchyma, rather than a generalized disruption of hypothalamic or peripheral endocrinology. The involvement of a specific glucose transporter in this deficit provides a new target for the design of AD therapies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neurobiolaging.2020.10.001

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Aβ induces a decrease in glucose uptake by reducing the availability of GLUT1, which amplifies the decrease in glycolysis.

    “In turn, A β , in a vicious circle, induces a decrease in glucose uptake, notably by reducing the availability of GLUT1, the plasma membrane transporter of glucose, which amplifies the decrease in glycolysis (Hendrix et al., 2021; Tarczyluk et al., 2015)”

    From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Hendrix et al., 2021

    The Results report reduced glucose uptake in Aβ42-tg mouse brains and less GLUT1 at the plasma membrane of Aβ-treated astrocytes. The paper links impaired GLUT1 localization to reduced cerebral glucose utilization, but does not report that this amplifies a decrease in glycolysis. Page numbers are not available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 84

  1. Ahn KC, Learman CR, Dunbar GL, Maiti P, Jang WC, Cha HC, Song MS, 2018 Characterization of impaired cerebrovascular structure in APP/PS1 mouse brains. Neuroscience 385, 246– 254. 29777753
  2. Alexander TC, Simecka CM, Kiffer F, Groves T, Anderson J, Carr H, Wang J, Carter G, Allen AR, 2018 Changes in cognition and dendritic complexity following intrathecal methotrexate and cytarabine treatment in a juvenile murine model. Behav. Brain Res 346, 21– 28. 29229546 PMC5860949
  3. Ashraf A, Fan Z, Brooks DJ, Edison P, 2015 Cortical hypermetabolism in MCI subjects: a compensatory mechanism? Eur. J. Nucl. Med. Mol. Imaging 42, 447– 458. 25267349
  4. Ayyadevara S, Ganne A, Hendrix RD, Balasubramaniam M, Shmookler Reis RJ, Barger SW, 2019 Functional assessments through novel proteomics approaches: application to insulin/IGF signaling in neurodegenerative disease. J. Neurosci. Methods 319, 40– 46. 30412730 PMC6451872
  5. Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S, 2011 Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch. Neurol 68, 51– 57. 20837822 PMC3023149
  6. Barros LF, Porras OH, Bittner CX, 2005 Why glucose transport in the brain matters for PET. Trends Neurosci. 28, 117– 119. 15749163
  7. Beeri MS, Silverman JM, Davis KL, Marin D, Grossman HZ, Schmeidler J, Purohit DP, Perl DP, Davidson M, Mohs RC, Haroutunian V, 2005 Type 2 diabetes is negatively associated with Alzheimer’s disease neuropathology. J. Gerontol. A Biol. Sci. Med. Sci 60, 471– 475. 15933386 PMC3163091
  8. Benzinger TL, Blazey T, Jack CR Jr., Koeppe RA, Su Y, Xiong C, Raichle ME, Snyder AZ, Ances BM, Bateman RJ, Cairns NJ, Fagan AM, Goate A, Marcus DS, Aisen PS, Christensen JJ, Ercole L, Hornbeck RC, Farrar AM, Aldea P, Jasielec MS, Owen CJ, Xie X, Mayeux R, Brickman A, McDade E, Klunk W, Mathis CA, Ringman J, Thompson PM, Ghetti B, Saykin AJ, Sperling RA, Johnson KA, Salloway S, Correia S, Schofield PR, Masters CL, Rowe C, Villemagne VL, Martins R, Ourselin S, Rossor MN, Fox NC, Cash DM, Weiner MW, Holtzman DM, Buckles VD, Moulder K, Morris JC, 2013 Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease. Proc. Natl. Acad. Sci. U S A 110, E4502– E4509. 24194552 PMC3839740
  9. Biessels GJ, Despa F, 2018 Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat. Rev. Endocrinol 14, 591– 604. 30022099 PMC6397437
  10. Borchelt DR, Davis J, Fischer M, Lee MK, Slunt HH, Ratovitsky T, Regard J, Copeland NG, Jenkins NA, Sisodia SS, Price DL, 1996 A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet. Anal 13, 159– 163. 9117892
  11. Botteri G, Salvado L, Guma A, Lee Hamilton D, Meakin PJ, Montagut G, Ashford MLJ, Ceperuelo-Mallafre V, Fernandez-Veledo S, Vendrell J, Calderon-Dominguez M, Serra D, Herrero L, Pizarro J, Barroso E, Palomer X, Vazquez-Carrera M, 2018 The BACE1 product sAPPbeta induces ER stress and inflammation and impairs insulin signaling. Metab. Clin. Exp 85, 59– 75. 29526536
  12. Boyle PJ, Kempers SF, O’Connor AM, Nagy RJ, 1995 Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus. N. Engl. J. Med 333, 1726– 1731. 7491135
  13. Bristol WR, Drill VA, 1952 Saline hydration and diuresis after adrenalectomy. Endocrinology 50, 677– 683. 12980076
  14. Caminiti SP, Ballarini T, Sala A, Cerami C, Presotto L, Santangelo R, Fallanca F, Vanoli EG, Gianolli L, Iannaccone S, Magnani G, Perani D, 2018 FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort. NeuroImage Clin. 18, 167– 177. 29387532 PMC5790816
  15. Carter SF, Chiotis K, Nordberg A, Rodriguez-Vieitez E, 2019 Longitudinal association between astrocyte function and glucose metabolism in autosomal dominant Alzheimer’s disease. Eur. J. Nucl. Med. Mol. Imaging 46, 348– 356. PMC6333721 30515545
  16. Chua LM, Lim ML, Chong PR, Hu ZP, Cheung NS, Wong BS, 2012 Impaired neuronal insulin signaling precedes Abeta42 accumulation in female AbetaPPsw/PS1DeltaE9 mice. J. Alzheimers Dis 29, 783– 791. 22337827
  17. Cohen AD, Price JC, Weissfeld LA, James J, Rosario BL, Bi W, Nebes RD, Saxton JA, Snitz BE, Aizenstein HA, Wolk DA, Dekosky ST, Mathis CA, Klunk WE, 2009 Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve. J. Neurosci 29, 14770– 14778. 19940172 PMC2810461
  18. Cornford EM, Hyman S, Cornford ME, Clare-Salzler M, 1995 Down-regulation of blood-brain glucose transport in the hyperglycemic nonobese diabetic mouse. Neurochem. Res 20, 869– 873. 7477681
  19. Dienel GA, 2012 Brain lactate metabolism: the discoveries and the controversies. J. Cereb. Blood Flow Metab 32, 1107– 1138. 22186669 PMC3390802
  20. Folch J, Ettcheto M, Busquets O, Sanchez-Lopez E, Castro-Torres RD, Verdaguer E, Manzine PR, Poor SR, Garcia ML, Olloquequi J, Beas-Zarate C, Auladell C, Camins A, 2018 The implication of the brain insulin receptor in late onset Alzheimer’s disease dementia. Pharmaceuticals (Basel, Switzerland) 11, 11. PMC5874707 29382127
  21. Friedland RP, Budinger TF, Ganz E, Yano Y, Mathis CA, Koss B, Ober BA, Huesman RH, Derenzo SE, 1983 Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F] fluorodeoxyglucose. J. Comput. Assist. Tomogr 7, 590– 598. 6602819
  22. Gabel MJ, Foster NL, Heidebrink JL, Higdon R, Aizenstein HJ, Arnold SE, Barbas NR, Boeve BF, Burke JR, Clark CM, Dekosky ST, Farlow MR, Jagust WJ, Kawas CH, Koeppe RA, Leverenz JB, Lipton AM, Peskind ER, Turner RS, Womack KB, Zamrini EY, 2010 Validation of consensus panel diagnosis in dementia. Arch. Neurol 67, 1506– 1512. 21149812 PMC3178413
  23. Gjedde A, 1981 More on the meaning of “blood-brain barrier”. Clin. Chem 27, 1474. 7273417
  24. Hassing LB, Johansson B, Nilsson SE, Berg S, Pedersen NL, Gatz M, McClearn G, 2002 Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer’s disease: a population-based study of the oldest old. Int. Psychogeriatr 14, 239– 248. 12475085
  25. Heitner J, Dickson D, 1997 Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology 49, 1306– 1311. 9371913
  26. Herholz K, Carter SF, Jones M, 2007 Positron emission tomography imaging in dementia. Br. J. Radiol 80 (Spec No 2), S160– S167. 18445746
  27. Hoffman JM, Welsh-Bohmer KA, Hanson M, Crain B, Hulette C, Earl N, Coleman RE, 2000 FDG PET imaging in patients with pathologically verified dementia. J. Nucl. Med 41, 1920– 1928. 11079505
  28. Horwood N, Davies DC, 1994 Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer’s disease. Virchows Arch. 425, 69– 72. 7921416
  29. Hwang JJ, Jiang L, Hamza M, Sanchez Rangel E, Dai F, Belfort-DeAguiar R, Parikh L, Koo BB, Rothman DL, Mason G, Sherwin RS, 2017 Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI Insight 2, e95913. PMC5846903 29046482
  30. Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S, Mauer J, Steculorum SM, Hampel B, Goldau J, Alber J, Forster CY, Eming SA, Schwaninger M, Ferrara N, Karsenty G, Bruning JC, 2016 Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. Cell 165, 882– 895. 27133169
  31. Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC, 2004 Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53, 474– 481. 14747300
  32. Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS, 2012 Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 61, 1444– 1454. 22362175 PMC3357272
  33. Kalaria RN, Harik SI, 1989 Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease. J. Neurochem 53, 1083– 1088. 2769254
  34. Kasper JM, Milton AJ, Smith AE, Laezza F, Taglialatela G, Hommel JD, Abate N, 2018 Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1. Int. J. Dev. Neurosci 64, 48– 53. 28373023 PMC5893149
  35. Kim EJ, Cho SS, Jeong BH, Kim YS, Seo SW, Na DL, Geschwind MD, Jeong Y, 2012 Glucose metabolism in sporadic Creutzfeldt-Jakob disease: a statistical parametric mapping analysis of (18) F-FDG PET. Eur. J. Neurol 19, 488– 493. 22050286 PMC3276684
  36. Kulas JA, Franklin W, Smith NA, Manocha GD, Puig KL, Nagamoto-Combs K, Hendrix RD, Taglialatela G, Barger SW, Combs CK, 2019 Ablation of amyloid precursor protein increases insulin Degrading enzyme levels and activity in brain and peripheral tissues. Am. J. Physiol. Endocrinol. Metab 316, E106– E120. 30422705 PMC6417684
  37. Kuznetsova E, Schliebs R, 2013 beta-Amyloid, cholinergic transmission, and cerebrovascular system - a developmental study in a mouse model of Alzheimer’s disease. Curr. Pharm. Des 19, 6749– 6765. 23530514
  38. Laforce R Jr., Tosun D, Ghosh P, Lehmann M, Madison CM, Weiner MW, Miller BL, Jagust WJ, Rabinovici GD, 2014 Parallel ICA of FDG-PET and PiBPET in three conditions with underlying Alzheimer’s pathology. NeuroImage Clin. 4, 508– 516. 24818077 PMC3984448
  39. Landau SM, Harvey D, Madison CM, Koeppe RA, Reiman EM, Foster NL, Weiner MW, Jagust WJ, 2011 Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol. Aging 32, 1207– 1218. 19660834 PMC2891865
  40. Lee YJ, Kim JE, Hwang IS, Kwak MH, Lee JH, Jung YJ, An BS, Kwon HS, Kim BC, Kim SJ, Kim JM, Hwang DY, 2013 Alzheimer’s phenotypes induced by overexpression of human presenilin 2 mutant proteins stimulate significant changes in key factors of glucose metabolism. Mol. Med. Rep 7, 1571– 1578. 23546527
  41. Leuzy A, Rodriguez-Vieitez E, Saint-Aubert L, Chiotis K, Almkvist O, Savitcheva I, Jonasson M, Lubberink M, Wall A, Antoni G, Nordberg A, 2018 Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer’s disease. Alzheimer’s & dementia. J. Alzheimers Assoc 14, 652– 663. 29268078
  42. Li B, Matter EK, Hoppert HT, Grayson BE, Seeley RJ, Sandoval DA, 2014 Identification of optimal reference genes for RT-qPCR in the rat hypothalamus and intestine for the study of obesity. Int. J. Obes 38, 192– 197. PMC3925437 23736358
  43. Liu W, Zhuo P, Li L, Jin H, Lin B, Zhang Y, Liang S, Wu J, Huang J, Wang Z, Lin R, Chen L, Tao J, 2017 Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture. Free Radic. Biol. Med 112, 174– 190. 28756309
  44. Liu Y, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX, 2008 Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett. 582, 359– 364. 18174027 PMC2247364
  45. Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF, Shan Q, 2011 Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IkappaB kinase beta/nuclear factor-kappaB-mediated inflammatory pathways in mice. Brain Behav. Immun 25, 1658– 1667. 21708244
  46. Lutz AJ, Pardridge WM, 1993 Insulin therapy normalizes GLUT1 glucose transporter mRNA but not immunoreactive transporter protein in streptozocin-diabetic rats. Metab. Clin. Exp 42, 939– 944. 8345816
  47. Lyra E Silva NM, Goncalves RA, Boehnke SE, Forny-Germano L, Munoz DP, De Felice FG, 2019 Understanding the link between insulin resistance and Alzheimer’s disease: Insights from animal models. Exp. Neurol 316, 1– 11. 30930096
  48. Makinoshima H, Takita M, Saruwatari K, Umemura S, Obata Y, Ishii G, Matsumoto S, Sugiyama E, Ochiai A, Abe R, Goto K, Esumi H, Tsuchihara K, 2015 Signaling through the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) axis is responsible for aerobic glycolysis mediated by glucose transporter in Epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. J. Biol. Chem 290, 17495– 17504. 26023239 PMC4498084
  49. Matioli M, Suemoto CK, Rodriguez RD, Farias DS, da Silva MM, Leite REP, Ferretti-Rebustini REL, Pasqualucci CA, Jacob WF, Grinberg LT, Nitrini R, 2017 Association between diabetes and causes of dementia: evidence from a clinicopathological study. Dement Neuropsychol. 11, 406– 412. 29354221 PMC5769999
  50. McCall AL, Millington WR, Wurtman RJ, 1982 Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus. Proc. Natl. Acad. Sci. U S A 79, 5406– 5410. 6752947 PMC346906
  51. McDonald JM, Cairns NJ, Taylor-Reinwald L, Holtzman D, Walsh DM, 2012 The levels of water-soluble and triton-soluble Abeta are increased in Alzheimer’s disease brain. Brain Res. 1450, 138– 147. 22440675 PMC3319647
  52. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, DeLucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T, 2005 Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47, 191– 199. 16039562 PMC1373682
  53. McMullan SM, Phanavanh B, Li GG, Barger SW, 2012 Metabotropic glutamate receptors inhibit microglial glutamate release. ASN Neuro. 4, e00094. 22770428 PMC3413012
  54. Merlini M, Meyer EP, Ulmann-Schuler A, Nitsch RM, 2011 Vascular beta-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAbeta mice. Acta Neuropathol. 122, 293– 311. 21688176 PMC3168476
  55. Mi Y, Qi G, Fan R, Qiao Q, Sun Y, Gao Y, Liu X, 2017 EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS. FASEB J. 31, 4998– 5011. 28739640
  56. Mooradian AD, Morin AM, 1991 Brain uptake of glucose in diabetes mellitus: the role of glucose transporters. Am. J. Med. Sci 301, 173– 177. 2000888
  57. Mortel KF, Wood S, Pavol MA, Meyer JS, Rexer JL, 1993 Analysis of familial and individual risk factors among patients with ischemic vascular dementia and Alzheimer’s disease. Angiology 44, 599– 605. 8342875
  58. Needham BE, Wlodek ME, Ciccotosto GD, Fam BC, Masters CL, Proietto J, Andrikopoulos S, Cappai R, 2008 Identification of the Alzheimer’s disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth. J. Pathol 215, 155– 163. 18393365
  59. Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, Kanba S, Kiyohara Y, 2011 Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology 77, 1126– 1134. 21931106
  60. Olsen JM, Sato M, Dallner OS, Sandstrom AL, Pisani DF, Chambard JC, Amri EZ, Hutchinson DS, Bengtsson T, 2014 Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1 translocation. J. Cell Biol 207, 365– 374. 25385184 PMC4226734
  61. Ossenkoppele R, Madison C, Oh H, Wirth M, van Berckel BN, Jagust WJ, 2014 Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function? Cereb. Cortex 24, 2210– 2218. 23537530 PMC4089385
  62. Ouanes S, Popp J, 2019 High cortisol and the risk of dementia and Alzheimer’s disease: a review of the literature. Front Aging Neurosci. 11, 43. 30881301 PMC6405479
  63. Pack AI, Galante RJ, Maislin G, Cater J, Metaxas D, Lu S, Zhang L, Von Smith R, Kay T, Lian J, Svenson K, Peters LL, 2007 Novel method for high-throughput phenotyping of sleep in mice. Physiol. Genomics 28, 232– 238. 16985007
  64. Parcon PA, Balasubramaniam M, Ayyadevara S, Jones RA, Liu L, Shmookler Reis RJ, Barger SW, Mrak RE, Griffin WST, 2018 Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs. Alzheimers Dement. 14, 230– 242. 28945989 PMC6613789
  65. Pardridge WM, Triguero D, Farrell CR, 1990 Downregulation of blood-brain barrier glucose transporter in experimental diabetes. Diabetes 39, 1040– 1044. 2384187
  66. Pruzin JJ, Nelson PT, Abner EL, Arvanitakis Z, 2018 Review: Relationship of type 2 diabetes to human brain pathology. Neuropathol. Appl. Neurobiol 44, 347– 362. 29424027 PMC5980704
  67. Pruzin JJ, Schneider JA, Capuano AW, Leurgans SE, Barnes LL, Ahima RS, Arnold SE, Bennett DA, Arvanitakis Z, 2017 Diabetes, hemoglobin A1C, and regional Alzheimer disease and infarct pathology. Alzheimer Dis. 31, 41– 47. PMC5321787 27755004
  68. Raffaitin C, Gin H, Empana JP, Helmer C, Berr C, Tzourio C, Portet F, Dartigues JF, Alperovitch A, Barberger-Gateau P, 2009 Metabolic syndrome and risk for incident Alzheimer’s disease or vascular dementia: the Three-City Study. Diabetes Care 32, 169– 174. 18945929 PMC2606808
  69. Reno CM, Puente EC, Sheng Z, Daphna-Iken D, Bree AJ, Routh VH, Kahn BB, Fisher SJ, 2017 Brain GLUT4 Knockout mice have impaired glucose tolerance, decreased insulin sensitivity, and impaired hypoglycemic counterregulation. Diabetes 66, 587– 597. 27797912 PMC5319720
  70. Roberts RO, Knopman DS, Cha RH, Mielke MM, Pankratz VS, Boeve BF, Kantarci K, Geda YE, Jack CR Jr., Petersen RC, Lowe VJ, 2014 Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation. J. Nucl. Med 55, 759– 764. 24652830 PMC4011952
  71. Schroeter M, Dennin MA, Walberer M, Backes H, Neumaier B, Fink GR, Graf R, 2009 Neuroinflammation extends brain tissue at risk to vital peri-infarct tissue: a double tracer [11C]PK11195- and [18F]FDG-PET study. J. Cereb. Blood Flow Metab 29, 1216– 1225. 19352400
  72. Simonovitch S, Schmukler E, Bespalko A, Iram T, Frenkel D, Holtzman DM, Masliah E, Michaelson DM, Pinkas-Kramarski R, 2016 Impaired autophagy in APOE4 astrocytes. J. Alzheimers Dis 51, 915– 927. 26923027
  73. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P, 1994 Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer’s disease. Ann. Neurol 35, 546– 551. 8179300
  74. Sokoloff L, 1977 Relation between physiological function and energy metabolism in the central nervous system. J. Neurochem 29, 13– 26. 407330
  75. Strachan MW, Deary IJ, Ewing FM, Ferguson SS, Young MJ, Frier BM, 2001 Acute hypoglycemia impairs the functioning of the central but not peripheral nervous system. Physiol. Behav 72, 83– 92. 11239984
  76. Trujillo-Estrada L, Nguyen C, da Cunha C, Cai L, Forner S, Martini AC, Ager RR, Prieto GA, Cotman CW, Baglietto-Vargas D, LaFerla FM, 2019 Tau underlies synaptic and cognitive deficits for type 1, but not type 2 diabetes mouse models. Aging Cell 18, e12919. 30809950 PMC6516168
  77. Tu Z, Keller MP, Zhang C, Rabaglia ME, Greenawalt DM, Yang X, Wang IM, Dai H, Bruss MD, Lum PY, Zhou YP, Kemp DM, Kendziorski C, Yandell BS, Attie AD, Schadt EE, Zhu J, 2012 Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets. PLoS Genet. 8, e1003107. 23236292 PMC3516550
  78. Vallerand AL, Perusse F, Bukowiecki LJ, 1987 Cold exposure potentiates the effect of insulin on in vivo glucose uptake. Am. J. Physiol 253, E179– E186. 3303966
  79. van de Nes JA, Kamphorst W, Ravid R, Swaab DF, 1998 Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer’s disease patients: amorphic plaques and cytoskeletal changes occur independently. Acta Neuropathol. 96, 129– 138. 9705127
  80. van de Nes JA, Konermann S, Nafe R, Swaab DF, 2006 Beta-protein/A4 deposits are not associated with hyperphosphorylated tau in somatostatin neurons in the hypothalamus of Alzheimer’s disease patients. Acta Neuropathol. 111, 126– 138. 16456666
  81. Vannucci SJ, Maher F, Simpson IA, 1997 Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 21, 2– 21. 9298843
  82. Wilson H, Pagano G, Politis M, 2019 Dementia spectrum disorders: lessons learnt from decades with PET research. J. Neural Transm. (Vienna) 126, 233– 251. 30762136 PMC6449308
  83. Zetterling M, Hillered L, Enblad P, Karlsson T, Ronne-Engstrom E, 2011 Relation between brain interstitial and systemic glucose concentrations after subarachnoid hemorrhage. J. Neurosurg 115, 66– 74. 21476811
  84. Zimmer ER, Parent MJ, Souza DG, Leuzy A, Lecrux C, Kim HI, Gauthier S, Pellerin L, Hamel E, Rosa-Neto P, 2017 [(18)F]FDG PET signal is driven by astroglial glutamate transport. Nat. Neurosci 20, 393– 395. 28135241 PMC5378483

Cited by

Sorted by citations

Authors
Hendrix, R. D., Ou, Y., Davis, J. E., Odle, A. K., Groves, T. R., Allen, A. R., Childs, G. V., & Barger, S. W.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Central Arkansas Veterans Healthcare System (US)
Corresponding author
Barger, Steven W.
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2021-01
Volume
97
Pages
73-88
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2020.10.001
PMC
PMC7736209
OpenAlex
W3092590666
Cited by
33
References
7
Citations by year
2026: 3 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 3
FWCI
2.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, other-oa)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • National Center for Research Resources
  • Roy and Christine Sturgis Charitable Trust
  • National Institute on Aging
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
Alzheimer's disease, amyloid-beta, amyloid-beta 42, glucose transporter 1, astrocytes, membrane trafficking, brain glucose metabolism, glucose tolerance, diet-induced obesity, Western diet, insulin resistance, spatial memory, cerebral metabolic rate of glucose, blood glucose regulation, type 2 diabetes
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Blood Glucose, Brain, Diabetes Mellitus, Type 2, Female, Insulin, Male, Mice, Transgenic, Obesity, Peptide Fragments, Risk, Gene Expression, Amyloid beta-Peptides, Glucose Transporter Type 1

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