David Holtzman, M.D.

Professor of Neurology; Scientific Director of the Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis


David Holtzman is Professor, scientific director of the Hope Center for Neurological Disorders, Co-Director of the Knight ADRC, and former Chair of Neurology at Washington University. Some of his lab’s accomplishments include showing in part how APOE contributes to AD, development of plasma and CSF biomarkers for AD, demonstration that synaptic activity and sleep affect Aβ and tau levels in vivo, describing the effects of APOE, TREM2, and both the innate and adaptive immune response on tau-mediated neurodegeneration. Several of his honors include being a recipient of the Potamkin Prize and MetLife award for research on Alzheimer’s disease, the Rainwater Prize for outstanding innovation in neurodegenerative disease research, election to the National Academy of Medicine, and being appointed to the National Advisory Council of the NINDS and NIA. Holtzman has trained over 70 graduate students and post-doctoral fellows, many of whom have gone on to successful careers in academia and industry.

To learn more, visit the Holtzman Lab website.

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
2024 Jeffrey L. Morby Prize for Exceptional Research 2024

$201,250

Non-Invasive Delivery of IL-2 to the CNS for Local Expansion of Regulatory T Cells and Prevention of Neurodegeneration in Tauopathy 2024

$201,250

Microbiome Consortium: The Role of Gut Microbial Metabolism in Tau-Mediated Neurodegeneration 2023

$287,500

Fleming APOE Consortium: Role of APOE Isoforms in Immune Responses in a Model of Tauopathy 2022, 2023

$690,000

TREM2: Role in Modulating Amyloid Beta and Tau-Related Pathologies and Neurodegeneration 2017, 2019

$645,000

Understanding the Effect of APOE on Tau-Mediated Neurodegeneration 2017, 2018, 2020, 2021

$1,200,000

Characterization of Certain Human APOE Targeted Gene Replacement Mice 2016

$49,600

The Biological Impact of TREM Locus Mutations in Alzheimer’s Disease 2015

$500,000

Sleep and tauopathies: Effect of an anti-tau antibody 2013

$100,000

Mechanisms of Retinoid X Receptor-Mediated Abeta Clearance in Alzheimers’ Disease 2011

$100,000

Effect of Bexarotene on Abeta in APP Tg Mice Expressing ApoE3 and ApoE4 2011

$100,000

Oligomer Collaborative Projects 2006

$1,550,000

Core Facility for Abeta Microdialysis Drug Discovery Platform 2007, 2008, 2009

$278,238

Development of Tau Microdialysis as a Method to Study Tau Metabolism, Pathophysiology and Response to Treatment 2009

$100,000

Defining the Effects of Physiological Synaptic Activity on Abeta Levels: Implications for AD 2008

$100,000

Anti-APOE Antibodies 2010

$100,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Lin, P. B., & Holtzman, D. M. Current insights into apolipoprotein E and the immune response in Alzheimer’s disease, Immunological Reviews, October 24, 2024, Read More

Capocchi, J. K., Figueroa-Romero, C., Dunham, S. J. B., Faraci, G., Rothman, J. A., Whiteson, K. L., Seo, D. O., Holtzman, D. M., Grabrucker, S., Nolan, Y. M., Kaddurah-Daouk, R., & Jett, D. A. Symposium: What Does the Microbiome Tell Us about Prevention and Treatment of AD/ADRD?, The Journal of Neuroscience, October 9, 2024, Read More

Carling, G. K., Fan, L., Foxe, N. R., Norman, K., Wong, M. Y., Zhu, D., Corona, C., Razzoli, A., Yu, F., Yarahmady, A., Ye, P., Chen, H., Huang, Y., Amin, S., Sereda, R., Lopez-Lee, C., Zacharioudakis, E., Chen, X., Xu, J., Cheng, F., … Gan, L. Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model, Neuron, September 24, 2024, Read More

Chen, Y., & Holtzman, D. M. New insights into innate immunity in Alzheimer’s disease: from APOE protective variants to therapies, Trends in Immunology, September 14, 2024, Read More

Sun, Z., Kwon, J. S., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A. J., Valdez, C., Houlden, H., Karch, C. M., Bateman, R. J., Sato, C., Mennerick, S. J., Diamond, M. I., Kim, J., Tanzi, R. E., Holtzman, D. M., Yoo, A. S. Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming, Science, August 8, 2024, Read More

Janelidze, S., Barthélemy, N. R., Salvadó, G., Schindler, S. E., Palmqvist, S., Mattsson-Carlgren, N., Braunstein, J. B., Ovod, V., Bollinger, J. G., He, Y., Li, Y., Raji, C. A., Morris, J. C., Holtzman, D. M., Ashton, N. J., Blennow, K., Stomrud, E., Bateman, R. J., & Hansson, O. Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment, JAMA Neurology, July 28, 2024, Read More

10. Kloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., … Gate, D., … , Iadecola, C., Johnson, L. A., Kanekiyo, T., … Lamb, B.T., … Marcora, E., … Morganti, J. M., … Ramachandran, K. V., … Tsai, L. H., … Ulrich, J. D., van der Kant, R., … Wellington, C. L., … Zhao, N., Bu, G., Goate, A. M., Holtzman, D. M. Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference, Alzheimer's & Dementia, July 19, 2024, Read More

Zhu, Y., Self, W. K., & Holtzman, D. M. An emerging role for the gut microbiome in tauopathy, Neurotherapeutics, July 3, 2024, Read More

Xiong, C., Luo, J., Wolk, D. A., Shaw, L. M., Roberson, E. D., Murchison, C. F., Henson, R. L., Benzinger, T. L. S., Bui, Q., Agboola, F., Grant, E., Gremminger, E. N., Moulder, K. L., Geldmacher, D. S., Clay, O. J., Babulal, G., Cruchaga, C., Holtzman, D. M., Bateman, R. J., Morris, J. C., Schindler, S. E. Baseline levels and longitudinal changes in plasma Aβ42/40 among Black and white individuals, Nature Communications, July 2, 2024, Read More

Hou, J., Chen, Y., Cai, Z., Heo, G. S., Yuede, C. M., … Holtzman, D. M. & Colonna, M. Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model, Science Translational Medicine, April 3, 2024, Read More

Salvadó, G., Horie, K., Barthélemy, N. R., Vogel, J. W., Pichet Binette, A., Chen, C. D., Aschenbrenner, A. J., Gordon, B. A., Benzinger, T. L. S., Holtzman, D. M., Morris, J. C., Palmqvist, S., Stomrud, E., Janelidze, S., Ossenkoppele, R., Schindler, S. E., Bateman, R. J., & Hansson, O. Disease staging of Alzheimer’s disease using a CSF-based biomarker model, Nature Aging, March 21, 2024, Read More

Bosch, M. E., Dodiya, H. B., Michalkiewicz, J., Lee, C., Shaik, S. M., Weigle, I. Q., Zhang, C., Osborn, J., Nambiar, A., Patel, P., Parhizkar, S., Zhang, X., Laury, M. L., Mondal, P., Gomm, A., Schipma, M. J., Mallah, D., Butovsky, O., Chang, E. B., Tanzi, R. E., Gilbert, J. A., Holtzman, D. M. & Sisodia, S. S. Sodium oligomannate alters gut microbiota, reduces cerebral amyloidosis and reactive microglia in a sex-specific manner, Molecular Neurodegeneration, February 17, 2024, Read More

Ma, Q., Zhao, Z., Sagare, A. P., Wu, Y., Wang, M., Owens, N. C., Verghese, P. B., Herz, J., Holtzman, D. M., & Zlokovic, B. V. Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism, Molecular Neurodegeneration, October 19, 2018, Read More

Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E. M., Diamond, M. I., Lee, V. M., & Holtzman, D. M. In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice, Journal of Neuroscience, September 14, 2011, Read More

Andrew, R. J., Fernandez, C. G., Stanley, M., Jiang, H., Nguyen, P., Rice, R. C., Buggia-Prévot, V., De Rossi, P., Vetrivel, K. S., Lamb, R., Argemi, A., Allaert, E. S., Rathbun, E. M., Krause, S. V., Wagner, S. L., Parent, A. T., Holtzman, D. M., & Thinakaran, G. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzhiemer’s disease, Proceedings of the National Academy of Sciences of the United States of America, October 23, 2017, Read More

Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., Krasemann, S., Lichtenthaler, S. F., Müller, S. A., Colombo, A., Monasor, L. S., Tahirovic, S., Herms, J., Willem, M., Pettkus, N., Butovsky, O., Bartenstein, P., Edbauer, D., Rominger, A., Erturk, A., Grathwohl, S. A., Neher, J. J., Holtzman, D., Meyer-Leuhmann, M., & Haass, C. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE, Nature Neuroscience, February 1, 2019, Read More

Roh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J., & Holtzman, D. M. Disruption of the sleep-wake cycle and diurnal fluctuations of amyloid-beta in mice with Alzheimer’s disease pathology, Science Translational Medicine, September 5, 2012, Read More

Kang, J. E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. Amyloid beta dynamics are regulated by orexin and the sleep wake cycle, Science, November 13, 2009, Read More

Wang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., Butovsky, O., Artyomov, M., Ulrich, J. D., & Holtzman, D. M. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia, Neuron, April 7, 2021, Read More

Krasemann, S., Madore, C., Cialic, R., Baufeld, C., ... Ulrich, J. D., … Lemere, C., Ikezu, T., ... Holtzman, D. M. … Haass, C., Butovsky, O. The TREM2-APOE Pathway drives the transcriptional phenotype of dysfunctional microglia in Neurodegenerative Diseases, Immunity, September 19, 2017, Read More

Steele, J. W., Kim, S. H., Cirrito, J. R., Verges, D. K., Restivo, J. L., Westaway, D., Fraser, P., Hyslop, P. S., Sano, M., Bezprozvanny, I., Ehrlich, M. E., Holtzman, D. M., & Gandy, S. Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo, Molecular Neurodegeneration, December 17, 2009, Read More

Chen, Y., Song, S., Parhizkar, S., Lord, J., Zhu, Y., Strickland, M. R., Wang, C., Park, J., Tabor, G. T., Jiang, H., Li, K., Davis, A. A., Yuede, C. M., Colonna, M., Ulrich, J. D., & Holtzman, D. M. APOE3ch alters microglial response and suppresses Aβ-induced tau seeding and spread, Cell, December 11, 2023, Read More

Ulland, T. K., Song, W. M., Huang, S. C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., Loginicheva, E., Gilfillan, S., Cella, M., Virgin, H. W., Unanue, E. R., Wang, Y., Artyomov, M. N., Holtzman, D. M., & Colonna, M. TREM2 maintains Microglial metabolic fitness in Alzheimer’s Disease, Cell, August 10, 2017, Read More

Schindler, S. E., Cruchaga, C., Joseph, A., McCue, L., Farias, F. H. G., Wilkins, C. H., Deming, Y., Henson, R. L., Mikesell, R. J., Piccio, L., Llibre-Guerra, J. J., Moulder, K. L., Fagan, A. M., Ances, B. M., Benzinger, T. L. S., Xiong, C., Holtzman, D. M., & Morris, J. C. African Americans Have Differences in CSF Soluble TREM2 and Associated Genetic Variants, Neurology Genetics, March 4, 2021, Read More

Mahan, T. E., Wang, C., Bao, X., Choudhury, A., Ulrich, J. D., & Holtzman, D. M. Selective reduction of astrocyte apoE3 and apoE4 strongly reduces A beta accumulation and plaque-related pathology in a mouse model of amyloidosi, Molecular Neurodegeneration, February 2, 2022, Read More

Ulrich, J. D., & Holtzman, D. M. TREM2 Function in Alzheimer’s Disease and Neurodegeneration, ACS Chemical Neuroscience, February 8, 2016, Read More

Chen, X., Firulyova, M., Manis, M., Herz, J., Smirnov, I., Aladyeva, E., Wang, C., Bao, X., Finn, M. B., Hu, H., Shchukina, I., Kim, M. W., Yuede, C. M., Kipnis, J., Artyomov, M. N., Ulrich, J. D., & Holtzman, D. M. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy, Nature, March 8, 2023, Read More

Ulrich, J. D., Burchett, J. M., Restivo, J. L., Schuler, D. R., Verghese, P. B., Mahan, T. E., Landreth, G. E., Castellano, J. M., Jiang, H., Cirrito, J. R., & Holtzman, D. M. In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis, Molecular Neurodegeneration, April 19, 2013, Read More

Ulrich, J. D., Ulland, T. K., Mahan, T. E., Nyström, S., Nilsson, K. P., Song, W. M., Zhou, Y., Reinartz, M., Choi, S., Jiang, H., Stewart, F. R., Anderson, E., Wang, Y., Colonna, M., & Holtzman, D. M. APoE facilitates the microglia response to amyloid plaque pathology, Journal of Experimental Medicine, February 26, 2018, Read More

Ulrich, J. D., Ulland, T. K., Colonna, M., & Holtzman, D. M. Elucidating the role of TREM2 in Alzheimer’s Disease, Neuron, April 19, 2017, Read More

Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy, Proceedings of the National Academy of Sciences of the United States of America, October 9, 2017, Read More

Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., Cella, M., Grutzendler, J., DeMattos, R. B., Cirrito, J. R., Holtzman, D. M., & Colonna, M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques, Journal of Experimental Medicine, April 18, 2016, Read More

Liu, C. C., Zhao, N., Yamaguchi, Y., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., & Bu, G. Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid beta clearance and aggregation in Alzheimer’s disease, Science Translational Medicine, March 30, 2016, Read More

Liu, C. C., Hu, J., Zhao, N., Wang, J., Wang, N., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., & Bu, G. Astrocytic LRP1 Mediates Brain A beta Clearance and Impacts Amyloid Deposition, Journal of Neuroscience, April 12, 2017, Read More

Faraco, G., Hochrainer, K., Segarra, S. G., Schaeffer, S., Santisteban, M. M., Menon, A., Jiang, H., Holtzman, D. M., Anrather, J., & Iadecola, C. Dietary salt promotes cognitive impairment through tau phosphorylation, Nature, October 23, 2019, Read More

Schwetye, K. E., Cirrito, J. R., Esparza, T. J., Mac Donald, C. L., Holtzman, D. M., & Brody, D. L. Traumatic brain injury reduces solubl extracellular amyloid-beta in mice: a methodologically novel combined microdialysis-controlled cortical impact study, Neurobiology of Disease, December 1, 2010, Read More

Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. Amyloid-beta dynamics correlate with neurological status in the injured human brain, Science, August 29, 2008, Read More

Tran, H. T., LaFerla, F. M., Holtzman, D. M., & Brody, D. L. Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid beta accumulation and independently accelerates the development of tau abnormalities, Journal of Neuroscience, June 29, 2011, Read More

Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., Holtzman, D. M., Cirrito, J. R., & Colonna, M. TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model, Cell, March 12, 2015, Read More

Ulrich, J. D., Finn, M. B., Wang, Y., Shen, A., Mahan, T. E., Jiang, H., Stewart, F. R., Piccio, L., Colonna, M., & Holtzman, D. M. Altered microglial response to A beta plaques in APPPS1-21 mice heterozygous for TREM2, Molecular Neurodegeneration, June 3, 2014, Read More

Chen, X., & Holtzman, D. M. Emerging roles of innate and adaptive immunity in Alzheimer’s disease, Immunity, December 13, 2022, Read More

Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P. M., Remolina Serrano, J., Hoyle, R., & Holtzman, D. M. Microglia derived APOE-dependent neurodegneration in a tauopathy mouse model, Journal of Experimental Medicine, November 4, 2019, Read More

Gallardo, G., & Holtzman, D. M. Antibody Therapeutics targeting Abeta and Tau, Cold Spring Harbor Perspectives in Medicine, October 1, 2017, Read More

Mann, C. N., Devi, S. S., Kersting, C. T., Bleem, A. V., Karch, C. M., Holtzman, D. M., & Gallardo, G. Astrocytic α2-Na+/K+ ATPase inhibition suppresses astrocyte reactivity and reduces neurodegeneration in a tauopathy mouse model, Science Translational Medicine, February 16, 2022, Read More

Wilson, D. M., 3rd, Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. Hallmarks of neurodegenerative diseases, Cell, February 16, 2023, Read More

Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., Cella, M., Ulland, T. K., Zaitsev, K., Miyashita, A., Ikeuchi, T., Sainouchi, M., Kakita, A., Bennett, D. A., Schneider, J. A., Nichols, M. R., Beausoleil, S. A., Ulrich, J., Holtzman, D. M., Artyomov, M. N., & Colonna, M. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease, Nature Medicine, January 13, 2020, Read More

Stout, S. H., Babulal, G. M., Ma, C., Carr, D. B., Head, D. M., Grant, E. A., Williams, M. M., Holtzman, D. M., Fagan, A. M., Morris, J. C., & Roe, C. M. Driving cessation over a 24-hour period: dementia severity and cerebrospinal fluid markers, Alzheimer's & Dementia, May 1, 2018, Read More

Vos, S. J. B., Gordon, B. A., Su, Y., Visser, P. J., Holtzman, D. M., Morris, J. C., Fagan, A. M., & Benzinger, T. L. S. NIA-AA staging of preclinical Alzhiemer disease: discordance and concordance of CSF and imaging biomarkers, Neurobiology of Aging, April 4, 2016, Read More

Ances, B. M., Christensen, J. J., Teshome, M., Taylor, J., Xiong, C., Aldea, P., Fagan, A. M., Holtzman, D. M., Morris, J. C., Mintun, M. A., & Clifford, D. B. Cognitively unimpaired HIV-positive subjects do not have icreased C-11 PiB A case-control study, Neurology, July 13, 2010, Read More

Ovod, V., Ramsey, K. N., Mawuenyega, K. G., Bollinger, J. G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D. M., Morris, J. C., Benzinger, T., Fagan, A. M., Patterson, B. W., & Bateman, R. J. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis, Alzheimer's & Dementia, July 19, 2017, Read More

Da Mesquita, S., Papadopoulos, Z., Dykstra, T., Brase, L., Farias, F. G., Wall, M., Jiang, H., Kodira, C. D., de Lima, K. A., Herz, J., Louveau, A., Goldman, D. H., Salvador, A. F., Onengut-Gumuscu, S., Farber, E., Dabhi, N., Kennedy, T., Milam, M. G., Baker, W., Smirnov, I., Rich, S. S., Dominantly Inherited Alzheimer Network, Benitez, B. A., Karch, C. M., Perrin, R. J., Farlow, M., Chhatwal, J. P., Holtzman, D. M., Cruchaga, C., Harari, O., & Kipnis, J. Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy, Nature, April 28, 2021, Read More

Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., Nguyen, K., Poliani, P. L., Beatty, W. L., Chen, Y., Cao, S., Lin, K., Rodrigues, C., Ellebedy, A. H., Gilfillan, S., Brown, G. D., Holtzman, D. M., Brioschi, S., & Colonna, M. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways, Cell, October 27, 2022, Read More

Horie, K., Salvadó, G., Barthélemy, N. R., Janelidze, S., Li, Y., He, Y., Saef, B., Chen, C. D., Jiang, H., Strandberg, O., Pichet Binette, A., Palmqvist, S., Sato, C., Sachdev, P., Koyama, A., Gordon, B. A., Benzinger, T. L. S., Holtzman, D. M., Morris, J. C., Mattsson-Carlgren, N., … Bateman, R. J. CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease, Nature Medicine, July 13, 2023, Read More

Esparza, T. J., Zhao, H., Cirrito, J. R., Cairns, N. J., Bateman, R. J., Holtzman, D. M., & Brody, D. L. Amyloid beta oligomerization in Alzheimer’s dementia versus high pathology controls, Annals of Neurology, January 1, 2013, Read More

Lawler, P. E., Bollinger, J. G., Schindler, S. E., Hodge, C. R., Iglesias, N. J., Krishnan, V., Coulton, J. B., Li, Y., Holtzman, D. M., & Bateman, R. J. Apolipoprotein E O-glycosylation is associated with amyloid plaques and APOE genotype, Analytical Biochemistry, April 16, 2023, Read More

Leyns, C. E. G., Gratuze, M., Narasimhan, S., Jain, N., Koscal, L. J., Jiang, H., Manis, M., Colonna, M., Lee, V. M. Y., Ulrich, J. D., & Holtzman, D. M. TREM2 Function Impedes Tau Seeding in Neuritic Plaques, Nature Neuroscience, June 1, 2019, Read More

Self, W. K., & Holtzman, D. M. Emerging diagnostics and therapeutics for Alzheimer disease, Nature Medicine, September 4, 2023, Read More

Xiong, M., Wang, C., Gratuze, M., Saadi, F., Bao, X., Bosch, M. E., Lee, C., Jiang, H., Serrano, J. R., Gonzales, E. R., Kipnis, M., & Holtzman, D. M. Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy, Molecular Neurodegenration, March 16, 2023, Read More

Liao, F., Jiang, H., Srivatsan, S., Xiao, Q., Lefton, K. B., Yamada, K., Mahan, T. E., Lee, J. M., Shaw, A. S., & Holtzman, D. M. Effects of CD2-associated protein deficiency on amyloid-beta in neuroblastoma cells and in an APP transgenic mouse model., Molecular Neurodegeneration, March 19, 2015, Read More

Verges, D. K., Restivo, J. L., Goebel, W. D., Holtzman, D. M., & Cirrito, J. R. Opposing synaptic regulation of amyloid-beta metabolism by NMDA Receptors in vivo, Journal of Neuroscience, August 3, 2011, Read More

Lim, M. M., Xu, J., Holtzman, D. M., & Mach, R. H. Sleep deprivation differentially affects dopamine receptor subtypes in mouse striatum, NeuroReport, July 13, 2011, Read More

Yan, P., Bero, A. W., Cirrito, J. R., Xiao, Q., Hu, X., Wang, Y., Gonzales, E., Holtzman, D. M., & Lee, J. M. Characterizing the Appearance and Growth of Amyloid plaques in APP/PS1 Mice, Journal of Neuroscience, August 26, 2009, Read More

Roh, J. H., Jiang, H., Finn, M. B., Stewart, F. R., Mahan, T. E., Cirrito, J. R., Heda, A., Snider, B. J., Li, M., Yanagisawa, M., de Lecea, L., & Holtzman, D. M. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease, Journal of Experimental Medicine, November 24, 2014, Read More

Kim, J., Eltorai, A. E., Jiang, H., Liao, F., Verghese, P. B., Kim, J., Stewart, F. R., Basak, J. M., & Holtzman, D. M. Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of A beta amyloidosis, Journal of Experimental Medicine, November 19, 2012, Read More

Cao, C., Cirrito, J. R., Lin, X., Wang, L., Verges, D. K., Dickson, A., Mamcarz, M., Zhang, C., Mori, T., Arendash, G. W., Holtzman, D. M., & Potter, H. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer’s disease transgenic mice, Journal of Alzheimers Disease, July 1, 2009, Read More

Roh, J. H., & Holtzman, D. M. Is there a link between the sleep-wake cycle and Alzheimer’s pathology, Future Neurology, May 1, 2015, Read More

Garai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C. The binding of apolipoprotein E to oligomers and fibrils of amyloid-beta alters the kinetics of amyloid aggregation, Biochemistry, September 25, 2014, Read More

Long, J. M., & Holtzman, D. M. Alzhiemer’s Disease: an update on pathobiology and treatment strategies, Cell, September 26, 2019, Read More

Zeng, C., Pan, F., Jones, L. A., Lim, M. M., Griffin, E. A., Sheline, Y. I., Mintun, M. A., Holtzman, D. M., & Mach, R. H. Evaluation of 5-ethynyl-2′-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system, Brain Research, March 1, 2010, Read More

Shi, Y., & Holtzman, D. M. Interplay between Innate immunity and Alzheimer’s disease: APOE ad TREM2 in the spotlight, Nature Reviews Immunology, August 23, 2018, Read More

Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J. M., & Holtzman, D. M. Neuronal activity regulates the regional vulnerability to amyloid-beta deposition, Nature Neuroscience, June 1, 2011, Read More

Chen, Y., Strickland, M. R., Soranno, A., & Holtzman, D. M. Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis, Neuron, November 10, 2020, Read More

Tabor, G. T., & Holtzman, D. M. Current status of amyloid-targeting immunotherapies for Alzheimer’s disease, Science Translational Medicine, November 8, 2023, Read More

Yan, P., Zhu, A., Liao, F., Xiao, Q., Kraft, A., Gonzales, E., Perez, R., Greenberg, S. M., Holtzman, D., & Lee, J. M. Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid angiopathy, Stroke, June 1, 2015, Read More

Parhizkar, S., & Holtzman, D. M. APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease, Seminars in Immunology, February 26, 2022, Read More

Wander, C. M., Tsujimoto, T. H. M., Ervin, J. F., Wang, C., Maranto, S. M., Bhat, V., Dallmeier, J. D., Wang, S. J., Lin, F. C., Scott, W. K., Holtzman, D. M., & Cohen, T. J. Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease, Acta Neuropathologica Communications, August 8, 2022, Read More

Holth, J. K., Mahan, T. E., Robinson, G. O., Rocha, A., & Holtzman, D. M. Altered sleep and EEG power in the P301S tau transgenic mouse model, Annals of Clinical and Translational Neurology, March 1, 2017, Read More

Liao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., Culver, J. P., Betensky, R., Wozniak, D. F., Hyman, B. T., & Holtzman, D. M. Anti-ApoE Antibody given after plaque onset decreases A beta accumulation and improves brain function in a mouse model of a beta amyloidosis, Journal of Neuroscience, May 21, 2014, Read More

Cadiz, M. P., Gibson, K. A., Todd, K. T., Nascari, D. G., Massa, N., Lilley, M. T., Olney, K. C., Al-Amin, M. M., Jiang, H., Holtzman, D. M., & Fryer, J. D. Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations, Journal of Experimental Medicine, January 16, 2024, Read More

Yin, Z., Rosenzweig, N., … Ikezu, T., … Tanzi, R., E., … Holtzman, D., M., & Butovsky, O. APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints, Nature Immunology, September 25, 2023, Read More

Drieu, A., Du, S., Kipnis, M., Bosch, M. E., Herz, J., Lee, C., Jiang, H., Manis, M., Ulrich, J. D., Kipnis, J., Holtzman, D. M., & Gratuze, M. Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration, Life Science Alliance, August 10, 2023, Read More

Wang, C., Nambiar, A., Strickland, M. R., Lee, C., Parhizkar, S., Moore, A. C., Musiek, E. S., Ulrich, J. D., & Holtzman, D. M. APOE-ε4 synergizes with sleep disruption to accelerate Aβ deposition and Aβ-associated tau seeding and spreading, Journal of Clinical Investigation, July 17, 2023, Read More

Gratuze, M., Schlachetzki, J. C. M., D'Oliveira Albanus, R., Jain, N., Novotny, B., Brase, L., Rodriguez, L., Mansel, C., Kipnis, M., O'Brien, S., Pasillas, M. P., Lee, C., Manis, M., Colonna, M., Harari, O., Glass, C. K., Ulrich, J. D., & Holtzman, D. M. TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4, Neuron, November 10, 2022, Read More

Margeta, M. A., Yin, Z., Madore, C., Pitts, K. M., Letcher, S. M., Tang, J., Jiang, S., Gauthier, C. D., Silveira, S. R., Schroeder, C. M., Lad, E. M., Proia, A. D., Tanzi, R. E., Holtzman, D. M., Krasemann, S., Chen, D. F., & Butovsky, O. Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma, Immunity, August 16, 2022, Read More

Tcw, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., Sikora, E., Andrews, E. J., Martini, A. C., Karch, C. M., Head, E., Holtzman, D. M., Zhang, B., Wang, M., Maxfield, F. R., Poon, W. W., & Goate, A. M. Cholesterol and matrisome pathways dysregulated in astrocytes and microglia, Cell, June 23, 2022, Read More

Capano, L. S., Sato, C., Ficulle, E., Yu, A., Horie, K., Kwon, J. S., Burbach, K. F., Barthélemy, N. R., Fox, S. G., Karch, C. M., Bateman, R. J., Houlden, H., Morimoto, R. I., Holtzman, D. M., Duff, K. E., & Yoo, A. S. Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons, Cell Stem Cell, June 2, 2022, Read More

Martens, Y. A., Zhao, N., Liu, C. C., Kanekiyo, T., Yang, A. J., Goate, A. M., Holtzman, D. M., & Bu, G. ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias, Neuron, March 16, 2022, Read More

Cable, J., Holtzman, D. M., Hyman, B. T., Tansey, M. G., Colonna, M., Kellis, M., Brinton, R. D., Albert, M., Wellington, C. L., Sisodia, S. S., & Tanzi, R. E. Alternatives to Amyloid for Alzheimer’s Disease Therapies-A Symposium Report, Annals of the New York Academy of Sciences, May 29, 2020, Read More

Huynh, T. V., Wang, C., Tran, A. C., Tabor, G. T., Mahan, T. E., Francis, C. M., Finn, M. B., Spellman, R., Manis, M., Tanzi, R. E., Ulrich, J. D., & Holtzman, D. M. Lack of hepatic apoE does not influence early A beta deposition: observations from a new APOE knock-in model, Molecular Neurodegeneration, October 17, 2019, Read More

Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., Rojas, J. C., Gallardo, G., Wang, K., Roh, J., Robinson, G., Finn, M. B., Jiang, H., Sullivan, P. M., Baufeld, C., Wood, M. W., Sutphen, C., McCue, L., Xiong, C., Del-Aquila, J.L., Morris, J.C., Cruchage, C., Alzheimer's Disease Neuroimaging Initiative, Fagan, A.M., Miller, B.L., Boxer, A.L., Seeley, W.W., Butovsky, O., Barres, B.B., Paul, S.M., & Holtzman, D.M. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy, Nature, September 28, 2017, Read More

Minter, M. R., Zhang, C., Leone, V., Ringus, D. L., Zhang, X., Oyler-Castrillo, P., Musch, M. W., Liao, F., Ward, J. F., Holtzman, D. M., Chang, E. B., Tanzi, R. E., & Sisodia, S. S. Antibiotic-induced perturbation in gut microbial diversity influences neuro-inflammation and amylodiosis in a murine model of Alzheimer’s disease, Scientific Reports, July 16, 2016, Read More

Musiek, E. S., & Holtzman, D. M. Three dimensions of the amyloid hypothesis: time, space, and ‘wingmen’, Nature Neuroscience, June 1, 2015, Read More

Musiek, E. S., Xiong, D. D., & Holtzman, D. M. Sleep, circadian rhythms and the pathogenesis of Alzheimer Disease, Experimental and Molecular Medicine, March 1, 2015, Read More

Musiek, E. S., Lim, M. M., Yang, G., Bauer, A. Q., Qi, L., Lee, Y., Roh, J. H., Ortiz-Gonzalez, X., Dearborn, J. T., Culver, J. P., Herzog, E. D., Hogenesch, J. B., Wozniak, D. F., Dikranian, K., Giasson, B. I., Weaver, D. R., Holtzman, D. M., & Fitzgerald, G. A. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration, Journal of Clinical Investigation, December 2, 2013, Read More

Musiek, E. S., & Holtzman, D. M. Origins of Alzheiemr’s disease: reconciling cerebrospinal fluid biomarker and neuropathology data regarding the temporal sequence of amyloid beta and tau involvement, Current Opinion in Neurology, December 1, 2012, Read More

McDonald, J. M., Cairns, N. J., Taylor-Reinwald, L., Holtzman, D., & Walsh, D. M. The levels of water-soluble and triton-soluble A beta are increased in Alzheimer’s disease brain, Brain Research, April 23, 2012, Read More

Bero, A. W., Bauer, A. Q., Stewart, F. R., White, B. R., Cirrito, J. R., Raichle, M. E., Culver, J. P., & Holtzman, D. M. Bidirectional relationship between functional connectivity and amyloid-beta deposition in mouse brain, Journal of Neuroscience, March 28, 2012, Read More