Julia Kofler, MD
Associate Professor of Pathology

Dr. Kofler
Dr. Kofler is a member of the Division of Neuropathology.
Office Location:
S701.3 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Contact Information:
Office Telephone: 412-624-6353
Fax: 412-624-5610
Email: koflerjk@upmc.edu

Education

  • MD - University of Vienna, 1997

Clinical Expertise

  • Surgical neuropathology
  • Autopsy neuropathology
  • Neurodegenerative diseases

Research Expertise

  • Diagnostic evaluation of neurodegenerative disorders and brain banking
    • Co-director and neuropathology core leader of the University of Pittsburgh Alzheimer's disease research center (ADRC)
    • Director, adult and pediatric neurodegenerative brain bank (Alzheimer's disease and related dementias, ALS, movement disorders, traumatic brain injury and chronic traumatic encephalopathy, leukodystrophies)
    • Director, Neurohistology laboratory
    • Neuropathology consultant for the Pittsburgh NIH NeuroBioBank
  • Genome-wide association studies have identified several novel risk genes for late-onset Alzheimer's disease (AD). Since the biological functions of many of these genes are only poorly characterized, it is uncertain how they mediate increased AD risk. To determine if these genes affect tau or amyloid deposition in the brain, we study the impact of risk alleles on AD pathology burden and comorbidities and have identified several associations of known risk factors with neurodegenerative pathologies. Additionally, we have identified several novel candidate genes associated with our pathology endophenotypes and are beginning to investigate the biological pathways underlying these associations. In a newly funded project, we are expanding these studies to identify genetic modifiers of white matter myelin and oligodendrocyte pathologies, which are frequently seen in AD brains, and will complement these studies by analyzing bulk and spatially defined gene expression levels in the white matter.
  • A more severe phenotype of AD is identified by the occurrence of psychosis. We are aiming to identify the pathobiology underlying this phenotype and have recently published findings that the psychosis phenotype is associated with higher phospho-Tau burden, higher prevalence of TDP-43 pathology and a shift in the synaptic proteome. In follow-up RNAseq studies using cell type proportion analysis, differential expression and Weighted Gene Correlation Network Analysis (WGCNA), we have identified reduced vulnerability of excitatory neurons and post-transcriptional synaptic compensation as possible mechanisms conferring resilience to psychosis. Ongoing studies are aimed to further dissect pathogenetic pathways by performing more comprehensive proteomics analyses, epigenetic analyses and single cell RNAseq studies.
  • Repetitive traumatic brain injury (concussions), such as sustained by contact sport participants, can lead to a neurodegenerative disease process called Chronic Traumatic Encephalopathy. While initial neuropathologic diagnostic criteria have been established for CTE, many unanswered questions remain about the frequency of CTE in symptomatic and asymptomatic athletes and about the spectrum of neuropathologic findings. To address these questions, we are developing a brain banking cohort of former contact sport participants, who will be followed longitudinally until death to collect information about their medical, trauma and cognitive histories. Postmortem examinations will allow us to better define the relationship between trauma exposure, cognitive trajectory and pathologic changes in the brain and to identify factors of resilience and vulnerability. In parallel, we are a participating site in the CONNECT-TBI consortium, a network of neuropathologists with expertise in neurodegenerative diseases, who will meet regularly for consensus reviews of brain autopsy cases with a TBI history and to refine diagnostic criteria.

NIH Research

View Dr. Kofler's NIH RePORT on nih.gov

Selected Publications

View Dr. Kofler's publications on PubMed
  1. Tulloch J, Leong L, Chen S, Keene CD, Millard SP, Shutes-David A, Lopez OL, Kofler J, Kaye JA, Woltjer R, Nelson PT, Neltner JH, Jicha GA, Galasko D, Masliah E, Leverenz JB, Yu CE, Tsuang D. APOE DNA methylation is altered in Lewy body dementia. Alzheimers Dement 2018;14:889-894
  2. Sang C, Maiti S, Fortunato RN, Kofler J, Robertson AM. A uniaxial testing approach for consistent failure in vascular tissues. J Biomechanical Engineering 2018;140:0610101-06101010
  3. McClain KL, Picarsic J, Chakraborty R, Zinn D, Lin H, Abhyankar H, Scull B, Shih A, Phaik Har Lim K, Eckstein O, Lubega J, Peters TL, Olea W, Burke T, Ahmed N, Hicks MJ, Tran B, Jones J, Dauser R, Jeng M, Baiocchi R, Schiff D, Goldman S, Heym KM, Wilson H, Carcamo B, Kumar A, Rodriguez-Galindo C, Whipple NS, Campbell P, Murdoch G, Kofler J, Heales S, Malone M, Woltjer R, Quinn JF, Orchard P, Kruer MC, Jaffe R, Manz MG, Lira SA, Parsons DW, Merad M, Man TK, Allen CE. CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions. Cancer 2018;124:4801-4821.
  4. Di Maio R, Hoffman EK, Rocha EM, Keeney MT, Sanders LH, De Miranda BR, Zharikov A, Van Laar A, McCoy J, Stepan A, Kofler JK, Burton EA, Alessi DR, Hastings TG, Greenamyre JT. A Central Role for LRRK2 in Idiopathic Parkinson Disease. Sci Transl Med 2018;10:eear5429
  5. Krivinko JM, Erickson SL, Ding Y, Sun Z, Penzes P, MacDonald ML, Yates NA, Ikonomovic MD, Lopez OL, Sweet RA, Kofler J. Synaptic protein compensation and resilience to psychosis in Alzheimer Disease. Am J Psych 2018;175:999-1009
  6. Minhas DS, Price JC, Laymon CM, Becker CR, Klunk WE, Tudorascu DL, Abrahamson EE, Hamilton RL, Kofler JK, Mathis CA, Lopez OL, Ikonomovic MD. Impact of partial volume correction on the regional correspondence between in vivo [C-11]PiB PET and postmortem measures of A? load. NeuroImage: Clinical 2018;19:182-189
  7. Besser LM, Kukull WA, Teylan MA, Bigio EH, Cairns NJ, Kofler JK, Montine TJ, Schneider JA, Nelson PT. The Revised National Alzheimer's Coordinating Center's Neuropathology Form-Available Data and New Analyses. J Neuropathol Exp Neurol 2018;77:717-726
  8. Pottier C, Zhou X, Perkerson RB 3rd, Baker M, Jenkins GD, Serie DJ, Ghidoni R, Benussi L, Binetti G, López de Munain A, Zulaica M, Moreno F, Le Ber I, Pasquier F, Hannequin D, Sánchez-Valle R, Antonell A, Lladó A, Parsons TM, Finch NA, Finger EC, Lippa CF, Huey ED, Neumann M, Heutink P, Synofzik M, Wilke C, Rissman RA, Slawek J, Sitek E, Johannsen P, Nielsen JE, Ren Y, van Blitterswijk M, DeJesus-Hernandez M, Christopher E, Murray ME, Bieniek KF, Evers BM, Ferrari C, Rollinson S, Richardson A, Scarpini E, Fumagalli GG, Padovani A, Hardy J, Momeni P, Ferrari R, Frangipane F, Maletta R, Anfossi M, Gallo M, Petrucelli L, Suh E, Lopez OL, Wong TH, van Rooij JGJ, Seelaar H, Mead S, Caselli RJ, Reiman EM, Noel Sabbagh M, Kjolby M, Nykjaer A, Karydas AM, Boxer AL, Grinberg LT, Grafman J, Spina S, Oblak A, Mesulam MM, Weintraub S, Geula C, Hodges JR, Piguet O, Brooks WS, Irwin DJ, Trojanowski JQ, Lee EB, Josephs KA, Parisi JE, Ertekin-Taner N, Knopman DS, Nacmias B, Piaceri I, Bagnoli S, Sorbi S, Gearing M, Glass J, Beach TG, Black SE, Masellis M, Rogaeva E, Vonsattel JP, Honig LS, Kofler J, Bruni AC, Snowden J, Mann D, Pickering-Brown S, Diehl-Schmid J, Winkelmann J, Galimberti D, Graff C, Öijerstedt L, Troakes C, Al-Sarraj S, Cruchaga C, Cairns NJ, Rohrer JD, Halliday GM, Kwok JB, van Swieten JC, White CL 3rd, Ghetti B, Murell JR, Mackenzie IRA, Hsiung GR, Borroni B, Rossi G, Tagliavini F, Wszolek ZK, Petersen RC, Bigio EH, Grossman M, Van Deerlin VM, Seeley WW, Miller BL, Graff-Radford NR, Boeve BF, Dickson DW, Biernacka JM, Rademakers R. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 2018;17:548-558
  9. Ritzel RM, Lai YJ, Crapser JD, Patel AR, Schrecengost A, Grenier JM, Mancini NS, Patrizz A, Jellison ER, Morales-Scheihing D, Venna VR, Kofler JK, Liu F, Verma R, McCullough LD. Aging alters the immunological response to ischemic stroke. Acta Neuropathol 2018;136:89-110
  10. La Joie R, Ayakta N, Seeley WW, Borys E, Boxer AL, DeCarli C, Doré V, Grinberg LT, Huang E, Hwang J, Ikonomovic MD, Jack Jr C, Jagust WJ, Jin L, Klunk WE, Kofler J, Lesman-Segev OH, Lockhart SN, Lowe VJ, Masters CL, Mathis CA, McLean CL, Miller BL, Mungas D, O'Neil JP, Olichney JM, Parisi JE, Petersen RC, Rosen HJ, Rowe CC, Spina S, Vemuri P, Villemagne VL, Murray ME, Rabinovici GD. Multi-site study of the relationships between ante mortem [11C]PIB-PET Centiloid values and post mortem measures of Alzheimer's disease neuropathology. Alz Dementia 2019;15:205-216.
  11. Barroeta-Espar I, Weinstock LD, Perez-Nievas BG, Meltzer AC, Siao Tick Chong M, Amaral AC, Murray ME, Moulder KL, Morris JC, Cairns NJ, Parisi JE, Lowe VJ, Petersen RC, Kofler J, Ikonomovic MD, López O, Klunk WE, Mayeux RP, Frosch MP, Wood LB, Gomez-Isla T. Distinct cytokine profiles in human brains resilient to Alzheimer's pathology. Neurobiol Dis 2019;121:327-337.
  12. Upadhyay Baskota S, Lopez OL, Greenamyre JT, Kofler J. Spectrum of Tau Pathologies in Huntington's disease. Laboratory Invest 2019;99:1068-77.
  13. Pottier C, Ren Y, Perkerson RB 3rd, Baker M, Jenkins GD, van Blitterswijk M, DeJesus-Hernandez M, van Rooij JGJ, Murray ME, Christopher E, McDonnell SK, Fogarty Z, Batzler A, Tian S, Vicente CT, Matchett B, Karydas AM, Hsiung GR, Seelaar H, Mol MO, Finger EC, Graff C, Öijerstedt L, Neumann M, Heutink P, Synofzik M, Wilke C, Prudlo J, Rizzu P, Simon-Sanchez J, Edbauer D, Roeber S, Diehl-Schmid J, Evers BM, King A, Mesulam MM, Weintraub S, Geula C, Bieniek KF, Petrucelli L, Ahern GL, Reiman EM, Woodruff BK, Caselli RJ, Huey ED, Farlow MR, Grafman J, Mead S, Grinberg LT, Spina S, Grossman M, Irwin DJ, Lee EB, Suh E, Snowden J, Mann D, Ertekin-Taner N, Uitti RJ, Wszolek ZK, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Hodges JR, Piguet O, Geier EG, Yokoyama JS, Rissman RA, Rogaeva E, Keith J, Zinman L, Tartaglia MC, Cairns NJ, Cruchaga C, Ghetti B, Kofler J, Lopez OL, Beach TG, Arzberger T, Herms J, Honig LS, Vonsattel JP, Halliday GM, Kwok JB, White CL 3rd, Gearing M, Glass J, Rollinson S, Pickering-Brown S, Rohrer JD, Trojanowski JQ, Van Deerlin V, Bigio EH, Troakes C, Al-Sarraj S, Asmann Y, Miller BL, Graff-Radford NR, Boeve BF, Seeley WW, Mackenzie IRA, van Swieten JC, Dickson DW, Biernacka JM, Rademakers R. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD. Acta Neuropathol 2019;137:879-899.
  14. Wang L, Ying J, Fan P, Weamer EA, DeMichele-Sweet MAA, Lopez OL, Kofler JK, Sweet RA. Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients. Am J Geriatr Psychiatry. 2019;27:908-917
  15. Mann JR, Gleixner AM, Mauna JC, Gomes E, DeChellis-Marks MR, Needham PG, Copley KE, Hurtle B, Portz B, Pyles NJ, Guo L, Calder CB, Wills ZP, Pandey UB, Kofler JK, Brodsky JL, Thathiah A, Shorter J, Donnelly CJ. RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43. Neuron. 2019;102:321-338.
  16. Cai W, Dai X, Chen J, Zhao J, Xu M, Zhang L, Yang B, Zhang W, Rocha M, Nakao T, Kofler J, Shi Y, Stetler RA, Hu X, Chen H. STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice. JCI Insight 2019;4(20):e131355
  17. Lefterov I, Wolfe CM, Fitz NF, Nam KN, Letronne F, Biedrzycki RJ, Kofler J, Han X, Wang J, Schug J, Koldamova R. APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain. Alz Res Ther 2019;11:113.
  18. Rocha EM, De Miranda BR, Castro S, Drolet R, Hatcher NG, Yao L, Smith SM, Keeney MT, Di Maio R, Kofler J, Hastings TG, Greenamyre JT. LRRK2 inhibition prevents endolysosomal deficits seen in human Parkinson's disease. Neurobiol Dis 2019;134:104626
  19. Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Huentelman MJ, Beach TG, Caselli RJ, Chen Y, Su Y, Myers AJ, Hardy J, Paul Vonsattel J, Younkin SG, Bennett DA, De Jager PL, Larson EB, Crane PK, Keene CD, Kamboh MI, Kofler JK, Duque L, Gilbert JR, Gwirtsman HE, Buxbaum JD, Dickson DW, Frosch MP, Ghetti BF, Lunetta KL, Wang LS, Hyman BT, Kukull WA, Foroud T, Haines JL, Mayeux RP, Pericak-Vance MA, Schneider JA, Trojanowski JQ, Farrer LA, Schellenberg GD, Beecham GW, Montine TJ, Jun GR; Alzheimer's Disease Genetics Consortium. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Comm 2020;11:667.
  20. Blasco MP, Chauhan A, Honarpisheh P, Ahnstedt H, d'Aigle J, Ganesan A, Ayyaswamy S, Blixt F, Venable S, Major A, Durgan D, Haag A, Kofler J, Bryan R, McCullough LD, Ganesh BP. Age-dependent Involvement of Gut Mast Cells and Histamine in Post-Stroke Inflammation. J Neuroinflammation 2020;17:160
  21. Weinstock NI, Shin D, Dhimal N, Hong X, Irons EE, Silvestri NJ, Reed CB, Nguyen D, Sampson O, Cheng YC, Lau JTY, Bongarzone ER, Kofler J, Escolar ML, Gelb MH, Wrabetz L, Feltri ML. Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction. Neuron 2020;107:65-81.
  22. Hudobenko J, Ganesh BP, Jiang J, Mohan EC, Lee S, Sheth S, Morales D, Zhu L, Kofler JK, Pautler RG, McCullough LD, Chauhan A. Growth Differentiation factor-11 Supplementation Improves Survival and Promotes Recovery After Ischemic Stroke in Aged Mice. Aging 2020;12:8049-8066
  23. Patrizz A, Doran SJ, Chauhan A, Ahnstedt H, Roy-O'Reilly M, Lai YJ, Weston G, Tarabishy S, Patel AR, Verma R, Staff I, Kofler JK, Li J, Liu F, Ritzel RM, McCullough LD. EMMPRIN/CD147 Plays a Detrimental Role in Clinical and Experimental Ischemic Stroke. Aging 2020;12:5121-5139
  24. Lopez OL, Kofler J, Chang Y, Berman SB, Becker JT, Sweet RA, Nadkarni N, Patira R, Kamboh MI, Cohen AD, Snitz BE, Kuller LH, Klunk WE. Relationship between hippocampal sclerosis, TDP-43, and the duration of the symptoms of dementia of Alzheimer's disease patients. Ann Clin Transl Neurol 2020;7:1546-1556
  25. Gireud-Goss M, Reyes S, Tewari R, Patrizz A, Howe MD, Kofler J, Waxham MN, McCullough LD, Bean AJ. The ubiquitin ligase UBE4B regulates amyloid precursor protein ubiquitination, endosomal trafficking, and amyloid ?42 generation and secretion. Mol Cell Neurosci 2020;108:103542.
  26. Ikonomovic MD, Buckley CJ, Abrahamson EE, Kofler JK, Mathis CA, Klunk WE, Farrar G. Post-mortem analyses of PiB and flutemetamol in diffuse and cored amyloid-? plaques in Alzheimer's disease. Acta Neuropathol 2002;140:463-476.
  27. Bu F, Munshi Y, Furr JW, Min JW, Qi L, Patrizz A, Spahr ZR, Urayama A, Kofler JK, McCullough LD, Li J. Activation of Neuronal Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1) Improves Post-Stroke Recovery and Axonal Plasticity in Mice. J Neurochem 2020, Sep 22 (Epub ahead of print)
  28. Ramesh N, Daley EL, Gleixner AM, Mann JR, Kour S, Mawrie D, Anderson EN, Kofler J, Donnelly CJ, Kiskinis E, Pandey UB. RNA dependent suppression of C9orf72 ALS/FTD associated neurodegeneration by Matrin-3. Acta Neuropathol Comm 2020;8:177
  29. Stepler KE, Mahoney ER, Kofler J, Hohman TJ, Lopez OL, Robinson RAS. Inclusion of African American/black adults in a pilot brain proteomics study of Alzheimer's disease. Neurobiol Dis 2020;146:105129
  30. Smith DH, Dollé JP, Ameen-Ali KE, Bretzin A, Cortes E, Crary JF, Dams-O'Connor K, Diaz-Arrastia R, Edlow BL, Folkerth R, Hazrati LN, Hinds SR, Iacono D, Johnson VE, Keene CD, Kofler J, Kovacs GG, Lee EB, Manley G, Meaney D, Montine T, Okonkwo DO, Perl DP, Trojanowski JQ, Wiebe DJ, Yaffe K, McCabe T, Stewart W. COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI). Acta Neuropathol Comm 2021;9:32
  31. Walker JM, Richardson TE, Farrell K, Iida MA, Foong C, Shang P, Attems J, Ayalon G, Beach TG, Bigio EH, Budson A, Cairns NJ, Corrada M, Cortes E, Dickson DW, Fischer P, Flanagan ME, Franklin E, Gearing M, Glass J, Hansen LA, Haroutunian V, Hof PR, Honig L, Kawas C, Keene CD, Kofler J, Kovacs GG, Lee EB, Lutz MI, Mao Q, Masliah E, McKee AC, McMillan CT, Mesulam MM, Murray M, Nelson PT, Perrin R, Pham T, Poon W, Purohit DP, Rissman RA, Sakai K, Sano M, Schneider JA, Stein TD, Teich AF, Trojanowski JQ, Troncoso JC, Vonsattel JP, Weintraub S, Wolk DA, Woltjer RL, Yamada M, Yu L, White CL, Crary JF. Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy. J Neuropathol Exp Neurol. 2021;80:102-111
  32. Anderson EN, Morera AA, Kour S, Cherry JD, Ramesh N, Gleixner A, Schwartz JC, Ebmeier C, Old W, Donnelly CJ, Cheng JP, Kline AE, Kofler J, Stein TD, Pandey UB. Traumatic injury compromises nucleocytoplasmic transport and leads to TDP-43 pathology. Elife 2021 May 26
  33. Rafael Guimarães T, Swanson E, Kofler J, Thathiah A. G protein-coupled receptor kinases are associated with Alzheimer's disease pathology. Neuropathol Appl Neurobiol 2021 Jun 23 (published online ahead of print)
  34. Dufour BD, Albores-Gallo L, Luna-Muñoz J, Hagerman R, Miquelajauregui A, Buriticá E, Saldarriaga W, Pacheco-Herrero M, Yris Silvestre-Sosa A, Mazefsky C, Gastgeb H, Kofler J, Casanova M, Hof PR, London E, Hagerman P, Martínez-Cerdeño V. Hispano-American Brain Bank on Neurodevelopmental Disorders: An initiative to promote brain banking, research, education, and outreach in the field of neurodevelopmental disorders. Brain Pathol 2021 Sep 13 (published online ahead of print)
  35. Iida MA, Farrell K, Walker JM, Richardson TE, Marx GA, Bryce CH, Purohit D, Ayalon G, Beach TG, Bigio EH, Cortes EP, Gearing M, Haroutunian V, McMillan CT, Lee EB, Dickson DW, McKee AC, Stein TD, Trojanowski JQ, Woltjer RL, Kovacs GG, Kofler JK, Kaye J, White CL 3rd, Crary JF. Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study. Acta Neuropathol Comm 2021;9:134
  36. McCullough LD, Roy-O'Reilly M, Lai YJ, Patrizz A, Xu Y, Lee J, Holmes A, Kraushaar DC, Chauhan A, Sansing LH, Stonestreet BS, Zhu L, Kofler J, Lim YP, Reddy Venna V. Exogenous inter-? inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice. J Clin Invest 2021 Sep 1 (published online ahead of print)