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Shannon L Macauley, PhD


760 Press Ave, Healthy Kentucky Research Building 136, Lexington, KY 40536


  • Associate Professor

College Unit(s)



Biography and Education


BA, Biology & Psychology, Middlebury College, Middlebury, VT

PhD, Neuroscience, Washington University School of Medicine, St Louis, MO

Postdoctoral Fellowship, Internal Medicine, Washington University School of Medicine, St Louis, MO

Postdoctoral Fellowship, Neurology, Washington University School of Medicine, St Louis, MO


The goal of my laboratory is to understand how alterations in brain metabolism relate to sleep impairment, vascular dysfunction, and inflammation in Alzheimer’s disease. Ultimately, the goal is to leverage these findings as therapeutic targets for treating Alzheimer’s disease and other CNS disorders, like lysosomal storage diseases.

We use a translational approach that combines rodent models, non-human primates, and human data to explore how metabolic or vascular perturbations affect the progression of Alzheimer’s disease. For our rodent studies, we use a variety of in vivo techniques, including glucose clamps, in vivo microdialysis, in vivo biosensors, EEG/EMG recordings, and small animal neuroimaging to study the acute effects of metabolic challenges on Aβ/tau dynamics, cerebral metabolism, neuronal activity, neurovascular coupling, and sleep. We also use rodent models and non-human primates to investigate how different Alzheimer’s risk factors impact pathology, metabolism, brain network connectivity, and behavior, and whether pharmacological and non-pharmacological interventions targeting metabolic dysfunction reverse pathology and functional deficits in Alzheimer’s disease.

Selected Publications

  • Macauley SL, Stanley M, Caesar EE, Yamada SA, Raichle ME, Perez R, Mahan TE, Sutphen CL, Holtzman DM. Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. J Clin Invest. 2015 Jun;125(6):2463-7.
  • Harris RA, Tindale L, Lone A, Singh O, Macauley SL, Stanley M, Holtzman DM, Bartha R, and Cumming RC.  Aerobic glycolysis in the frontal cortex correlates with memory performance in wild-type mice but not the APP/PS1 mouse model of cerebral amyloidosis. J. Neurosci.  2016 Feb 10;36(6):1871-8.
  • Stanley M, Macauley SL, and Holtzman DM. Changes in insulin and insulin signaling in Alzheimer's disease: cause or consequence? J Exp Med. 2016 Jul 25;213(8):1375-85. 
  • Stanley M, Macauley SL, Caesar EE, Koscal LJ, Moritz W, Robinson GO, Roh J, Keyser J, Jiang H, and Holtzman DM. The effects of peripheral and central high insulin on brain insulin signaling and amyloid-beta in young and old APP/PS1 mice. J Neurosci. 2016 Nov 16;36(46):11704-11715.
  • Ju Y S, Ooms SJ, Sutphen C, Macauley SL, Zangrilli M, Jerome G, Fagan AM, Mignot E, Zempel JM, Claasssen JAHR, and Holtzman DM.  Slow wave sleep disruption increased cerebrospinal fluid amyloid-beta levels.  Brain. 2017 Aug 1;140(8):2104-2111.
  • Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018 Mar;14(3):168-181.
  • Day SE, Yang W, Stern J, Zhou X, Macauley SL, and Ma T. Glucagon-like peptide-1 cleavage product improves cognitive function in a mouse model of Down syndrome.  eNeuro. 2019 Mar/Apr;6(2).
  • Kavanagh K, Day SM, Pait MC, Mortiz WR, Newgard CB, Ilkayeva O, McClain DA, Macauley SL. Type-2-diabetes Alters CSF but not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys. Front Neurosci. 2019 Aug 28;13:843.
  • Carroll CM and Macauley SL. The interaction between sleep and metabolism in Alzheimer’s disease: cause or consequence of disease? Front Aging Neurosci. 2019 Sep 20;11:258.
  • Gibson EM, Bennet FC, Gillespie SM, Guler AD, Gutmann DH, Halpern CH, Kucenas SC, Kushida CA, Lemieux M, Liddelow S, Macauley SL, Li TQ, Quinn M, Roberts, LW, Saligrama N, Taylor K, Venkatesh H, Yalcin B, and Zuchero JB. How support of early career researchers can reset science in the post-COVID19 world. Cell. June 2020.
  • Frye BM, Craft S, Laitmer CS, Keene CD, Montine TJ, Register RC, Orr ME, Kavanagh K, Macauley SL, Shively CA. Aging related Alzheimer's disease-like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus). American Journal of Primatology. 2021. In press.
  • Damuka N, Orr ME, Bansode AH, Krizan I, Miller M, Lee J, Macauley SL, Whitlow CT, Mintz A, Craft S, Solingapuram Sai KK. Preliminary mechanistic insights of a brain-penetrant microtubule imaging PET ligand in a tau-knockout mouse model. EJNMMI Res. 2022 Jul 26;12(1):41. doi: 10.1186/s13550-022-00912-z. PMID: 35881263
  • Macauley SL, Grizzanti J, Stanley M, Caesar EE, Mortiz WR, Bice AR, Cruz-Diaz N, Carrol CM, Day SM, Constantino NJ, Mahan TE, Snipes JA, Orr TC, Culver JP, Remedi MS, Nichols CG, Karch CM, Cox LA, Diz DI, Bauer AQ, Holtzman DM,. Sulfonylureas target the neurovascular response to decrease Alzheimer’s pathology. BioRxiv. doi:
  • Day SM, Gironda SC, Clarke CW, Snipes JA, Nicol NI, Kamran H, Vaughan W, Weiner JL, Macauley SL. Ethanol exposure alters Alzheimer's-related pathology, behavior, and metabolism in APP/PS1 mice. Neurobiol Dis. 2023 Feb;177:105967. doi: 10.1016/j.nbd.2022.105967. Epub 2022 Dec 16. PMID: 36535550.
  • Grizzanti J, Moritz WR, Pait MC, Stanley M, Kaye SD, Carroll CM, ConstantinoNJ, Deitelzweig LJ, Snipes JA, Kellar D, Caesar EE, Pettit-Mee RJ, Day SM, Sens JP, Nicol NI, Dhillon J, Remedi MS, Kiraly DD, Karch CM, Nichols CG, Holtzman DM, Macauley SL. KATP channels are necessary for glucose-dependent increases inamyloid-β and Alzheimer's disease-related pathology. JCI Insight. 2023 May 2;8(10):e162454. doi: 10.1172/jci.insight.162454. PMID: 37129980; PMCID: PMC10386887.
  • Carroll CM, Stanley M, Raut RV, Constantino NJ, Irmen RE, Mitra A, Snipes JA, Raichle ME, Holtzman DM, Gould RW, Kishida KT, and Macauley SL. Acute hyper- and hypo-glycemia uncouples the metabolic cooperation between glucose and lactate to disrupt sleep. bioRxiv 2022.09.15.507967; doi:  
  • Lee S, Williams HC, Gorman AA,  Devanney NA, Harrison DA, Walsh AE, Goulding DS, Tuck T, Schwartz JL, Zajac DJ, Macauley SL, Estus S, TCW J, Johnson LA,  Morganti JM. APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes. bioRxiv 2023.02.06.527204; doi:
  • Pait MC, Kaye SD, Su Y, Kumar A, Singh S, Gironda SC, Vincent S, Anwar M, Carroll CM, Snipes JA, Lee J, Furdui CM, Deep G, Macauley SL. Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EVISF) reveals sex-dependent changes in microglial EV contents in response to Aβ pathology. bioRxiv,
  • Rhea EM, Leclerc M, Yassine HM, Capuano AW, Tong H, Petyuk VA, Macauley SL, Fioramonti X, Carmichael O, Calon F, and Arvanitakis Z. State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer’s Disease. Aging and Disease. 2023.