Neuropathology Core

Edwin Monuki, MD, PhD, Professor and Chair, Pathology; Joint Appointment, Developmental & Cell Biology

Edwin Monuki, MD, PhD, Professor and Chair, Pathology; Joint Appointment, Developmental & Cell Biology

What caused my loved one to have dementia?  This may be the most important question the Neuropathology Core addresses after a research participant passes away and donates his or her brain to science.

The Neuropathology Core, led by Dr. Edwin Monuki, aims to uncover the cellular and molecular mechanisms underlying Alzheimer’s disease and related disorders. In addition to providing families with a definitive diagnosis, brain donation enables scientists to conduct innumerable studies that explore the neuropathological changes that occur during aging and dementia and the relationship of those changes to the cognitive, functional, and behavioral symptoms present in life.

During an autopsy of the donated brain, neuropathologists examine the tissue, looking for the hallmark signs of Alzheimer’s disease – amyloid plaques and neurofibrillary tangles – as well as other pathological changes that may have contributed to the clinical symptoms. All brain tissue and other biological specimens are stored in the UCI ADRC Tissue Repository managed by the Neuropathology Core.

Additionally, the Neuropathology Core is responsible for distributing tissue and other biological specimens to researchers and promoting cross-center collaborations to maximize use of these precious samples.  Every ADRC clinician and investigator involved in handling brain tissue and biological specimens does so with great care, highly aware of the invaluable gift research volunteers are making. To learn more about brain donation, click here.

Leadership:

Brain Donation Program

1211 Gillespie Neuroscience
Irvine, CA 92697-4540
Telephone: 949.824.5032
Pager: 714.506.4004
Fax: 949.824.2071

Tissue Request for Investigators

The National Alzheimer’s Coordinating Center (NACC) has a neuropathology and biospecimen resource locator tool to assist investigators with the search of all stored and banked autopsy materials related to ADC participants.

With NACC’s tissue resource locator, you can determine which Alzheimer’s Disease Centers (ADCs) have postmortem specimens that may be available for sharing.

Resource Locator Tool

To date, the NP Core has collected a total of 1,630 brain autopsy cases.  In the last 5 years, the NP Core did not miss a single brain donation despite the COVID-19 pandemic, collecting 211 brains, fulfilling 189 requests (a projected doubling over the previous 5-year cycle), and supporting 41 publications and 64 grants, including 54 NIH grants.

Publications

Sample of Core Publications

Aslam MM, Dang LT, Shi R, Fan KH, Cheema AN, Xicota L, Minhas D, Luo W, Zafari N, Acharya V, Feingold E, Krinsky-McHale S, Laymon CM, Cohen A, Handen BL, Christian BT, Head E, Mapstone ME; Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS); Lee JH, Cruchaga C, Kamboh MI. Genome-wide association analyses identify candidate loci for amyloid imaging and plasma biomarkers in adults with Down syndrome. Alzheimers Dement. 2025 Jul;21(7):e70358. doi: 10.1002/alz.70358 (opens in new tab). PMID: 40667702 (opens in new tab). PMCID: PMC12265027 (opens in new tab).

Bertholim-Nasciben L, Nuytemans K, Van Booven D, Rajabli F, Moura S, Ramirez AM, Parker GS, Dykxhoorn DM, Wang L, Scott WK, Davis DA, Vontell RT, McInerney KF, Cuccaro ML, Byrd GS, Haines JL, Gearing M, Adams LD, Pericak-Vance MA, Young JI, Griswold AJ, Vance JM. Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers. Alzheimers Dement. 2025 Jul;21(7):e70500. doi: 10.1002/alz.70500 (opens in new tab). PMID: 40704449 (opens in new tab). PMCID: PMC12287753 (opens in new tab).

Blurton-Jones M, Davtyan H, Chadarevian JP, Lakatos A, Lin S, Hasselmann J, Nguyen J, Duong D, Capocchi J, Lahian A, Mansour K, Eskandari-Sedighi G, Tu C, Shabestari SK, Wu F, Shantaraman A, Mgerian M, Lim T, Mai A, Le L, Agababian A, Head E, Datta SR, Seyfried N. Brain wide engraftment of human monocytes induces neurodegeneration and cognitive dysfunction. Res Sq [Preprint]. 2025 Oct 10:rs.3.rs-7762816. doi: 10.21203/rs.3.rs-7762816/v1 (opens in new tab). PMID: 41282056 (opens in new tab). PMCID: PMC12632712 (opens in new tab).

Caceres-Palomo L, Sanchez-Mejias E, Trujillo-Estrada L, Perez-Moreno JJ, Lopez-Oliva E, Lim TE, DeFlitch L, Chang SH, Kampman L, Corces MR, Blurton-Jones M, Moreno-Gonzalez I, Pascual A, Vitorica J, Garcia-Leon JA, Gutierrez A. Human iPSC-derived APOE4/4 Alzheimer´s disease astrocytes exhibit a senescent and pro-inflammatory state that compromises neuronal support. J Neuroinflammation. 2025 Dec 12;23(1):9. doi: 10.1186/s12974-025-03607-z (opens in new tab). PMID: 41388301 (opens in new tab). PMCID: PMC12781401 (opens in new tab).

Chakkarai S, Sadowski M, Yang Q, Ray A, Wang R, Thomas LF, Fuentes RP, Tabar MS, Cui B, Jian X, Nyquist PA, Gill D, Aiello AE, Montine TJ, Bukhari S, Rogalski E, Edland SE, Haan ME, Kawas CH, Corrada MM, Salardini A, Chen ZZ, Himali JJ, Satizabal CL, Gerszten RE, Åsvold BO, Fornage M, Cruchaga C, Habes M, Chasman DI, Launer LJ, Flanagan ME, Brumpton BM, Georgakis MK, Zaitlen N, Ruiz A, Debette S, Seshadri S, Sargurupremraj M. Cross-tissue omics-guided drug repurposing triangulates novel targetable mechanisms for Alzheimer's disease and candidate genetic biomarkers for treatment stratification. Res Sq [Preprint]. 2025 Aug 5:rs.3.rs-7279662. doi: 10.21203/rs.3.rs-7279662/v1 (opens in new tab). PMID: 40799764 (opens in new tab). PMCID: PMC12340895 (opens in new tab).

de Flores R, Canada KL, Brown T, Gervais NJ, Maass A, Rådman G, Shine J, Tucker HL, Molloy EN, Adams JN, Reinke MB, Bakker A, Berron D, Dalton MA, Kennedy KM, LaJoie R, Mueller SG, Ofen N, Olsen RK, Raz N, Riggins T, Rodrigue KM, Stark C, Wang L, Wisse LEM, Yushkevich PA, Carr VA, Daugherty AM. Harmonized Protocol for Segmentation of the Hippocampal Tail on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG). bioRxiv [Preprint]. 2025 Nov 20:2025.11.20.689476. doi: 10.1101/2025.11.20.689476 (opens in new tab). PMID: 41332685 (opens in new tab). PMCID: PMC12667945 (opens in new tab).

Dorfschmidt L, White S, Gardner M, Bedford S, Ball G, Edwards AD, Gu Y, He Y, Huang H, Karandikar S, Kyriakopoulou V, Ouyuang M, Pulli EP, Raznahan A, Robinson EC, Romero-García R, Satterthwaite TD, Schabdach J, Sebenius I, Sha Z, Shinohara RT, Tuulari J, Vaghi MM, Vogel J, Váša F, Williams L, Zimmerman D; Lifespan Brain Chart Consortium; Warrier V, Wagstyl K, Bullmore ET, Bethlehem RAI, Seidlitz J, Alexander-Bloch A. Charting structural brain asymmetry across the human lifespan. bioRxiv [Preprint]. 2025 Jul 24:2025.07.21.665924. doi: 10.1101/2025.07.21.665924 (opens in new tab). PMID: 40777274 (opens in new tab). PMCID: PMC12330520 (opens in new tab).

Edwards NC, Lao PJ, Alshikho MJ, Ericsson OM, Rizvi B, Petersen ME, O'Bryant S, Flores-Aguilar L, Simoes S, Mapstone M, Tudorascu DL, Janelidze S, Hansson O, Handen BL, Christian BT, Lee JH, Lai F, Rosas HD, Zaman S, Lott IT, Yassa MA; Alzheimer's Biomarkers Consortium–Down Syndrome (ABC‐DS) Investigators; Gutierrez J, Wilcock DM, Head E, Brickman AM. Alzheimer's disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome. Alzheimers Dement. 2025 Oct;21(10):e70726. doi: 10.1002/alz.70726 (opens in new tab). PMID: 41014048 (opens in new tab). PMCID: PMC12475832 (opens in new tab).

Ellis RJ, Airaud A, Jasodanand VH, Kowshik SS, Bellitti M, Kolachalama VB, Estiri H, Glymour MM, Dufouil C, Sperling RA, Bennett DA, Patel CJ; Alzheimer’s Disease Neuroimaging Initiative; Australian Imaging Biomarkers and Lifestyle flagship study of ageing. Prognostic performance across Alzheimer's biomarkers, multi-modal physiological measures, and clinical history in asymptomatic individuals. medRxiv [Preprint]. 2025 Nov 20:2025.11.19.25340533. doi: 10.1101/2025.11.19.25340533 (opens in new tab). PMID: 41332865 (opens in new tab). PMCID: PMC12668057 (opens in new tab).

Evans TE, Vilor-Tejedor N, Operto G, Falcon C, Hofman A, Ibáñez A, Seshadari S, Tan LCS, Weiner M, Alladi S, Anazodo U, Gispert JD; Alzheimer’s Disease Neuroimaging Initiative; Australian Imaging Biomarkers and Lifestyle flagship study of ageing; Adams HHH. Structural Brain Differences in the Alzheimer's Disease Continuum: Insights Into the Heterogeneity From a Large Multisite Neuroimaging Consortium. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Oct;10(10):1025-1036. doi: 10.1016/j.bpsc.2024.07.019 (opens in new tab). PMID: 39084525 (opens in new tab). PMCID: PMC12010407 (opens in new tab).

Fan KH, Shi R, Cheema AN, Dang LT, Xicota L, Krinsky-McHale S, Aslam MM, Zafari N, Acharya V, Feingold E, Laymon CM, Cohen A, Handen BL, Christian BT, Head E, Mapstone ME; Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS); Cruchaga C, Lee JH, Kamboh MI. Genome-wide association of tau neuroimaging and plasma biomarkers in adults with Down syndrome. Alzheimers Dement. 2025 Jul;21(7):e70398. doi: 10.1002/alz.70398 (opens in new tab). PMID: 40667715 (opens in new tab). PMCID: PMC12264832 (opens in new tab).

Fischer DL, Grinberg LT, Ahrendsen JT, Beach TG, Bieniek KF, Castellani RJ, Chkheidze R, Cobos I, Cohen M, Crary JF, Dickson DW, Dugger BN, Dunlop SR, Farrell K, Ghetti B, Haeri M, Harrison W, Head E, Hiniker A, Huang EJ, Huttner A, Jamshidi P, Kapasi A, Keene CD, Kofler J, Latimer CS, McKee AC, Mente K, Miller MB, Montine TJ, Morris M, Murray ME, Nelson PT, Newell KL, Perrin RJ, Ramani B, Reichard RR, Roy S, Schlachetzki JCM, Seeley WW, Serrano GE, Spina S, Teich AF, Wang SJ, Wisniewski T, Lee EB. Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers. Alzheimers Dement. 2025 Oct;21(10):e70734. doi: 10.1002/alz.70734 (opens in new tab). PMID: 41085158 (opens in new tab). PMCID: PMC12519528 (opens in new tab).

George GC, Keller SA, Abner E, Adar S, Alosco ML, Apostolova LG, Bakulski K, Barnes LL, Bateman JR, Batterman S, Beach TG, Bendlin BB, Bennett DA, Betthauser TJ, Brewer J, Buckingham W, Carrión CI, Chodosh J, Craft S, Croff R, Fabio A, Farias ST, Feldman EL, Goldstein F, Goutman SA, Green-Harris G, Henderson V, Karikari TK, Kofler J, Kucharska-Newton A, Lamar M, Lanata S, Lepping RJ, Lingler J, Lockhart S, Mahnken J, Marsh K, Mathew J, Mecca AP, Meyer O, Miller B, Morris J, Neugroschl J, O'Connor MK, Paulson H, Perrin RJ, Pettigrew C, Pierce A, Powell WR, Pyarajan S, Raji CA, Reiman E, Risacher S, Rissman R, Espivnosa PR, Sano M, Saykin AJ, Serrano GE, Singh V, Soldan A, Sultzer D, van Dyck CH, Whitmer R, Wisniewski T, Woltjer R, Yu M, Zhu CW, Kind AJH. The Neighborhoods Study: Examining the social exposome in Alzheimer's disease and related dementias. Alzheimers Dement. 2025 Nov;21(11):e70810. doi: 10.1002/alz.70810 (opens in new tab). PMID: 41230793 (opens in new tab). PMCID: PMC12613078 (opens in new tab).

Godrich D, Pasteris J, Martin ER, Kunkle B, Naj AC, Hamilton K, Wang H, Lee WP, Dumitrescu L, Hohman TJ, Mayeux R, Larson EB, Crane PK, Keene CD, Latimer C, Mukherjee S, Kofler J, Kamboh MI, Bennett DA, Molina-Porcel L, Schellenberg G, Pericak-Vance MA, Cuccaro M, Scott WK, Rundek T, Kukull W, Montine T, Beecham GW; Alzheimer's Disease Genetics Consortium (ADGC). Genome-wide association studies of TDP-43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B. Alzheimers Dement. 2025 Nov;21(11):e70760. doi: 10.1002/alz.70760 (opens in new tab). PMID: 41208712 (opens in new tab). PMCID: PMC12598407 (opens in new tab).

Kanakaraj P, Bogdanov S, Kim ME, Samir J, Gao C, Ramadass K, Rudravaram G, Newlin NR, Archer D, Hohman TJ, Jefferson AL, Morgan VL, Roche A, Englot DJ, Resnick SM, Held LLB, Cutting L, Barquero LA, D'Archangel MA, Nguyen TQ, Humphreys KL, Niu Y, Vinci-Booher S, Cascio CJ; HABS-HD Study Team; Alzheimer’s Disease Neuroimaging Initiative; BIOCARD Study Team; Li Z, Vandekar SN, Zhang P, Gore JC, Forkel SJ, Landman BA, Schilling KG. Lifespan Trajectories of Asymmetry in White Matter Tracts. bioRxiv [Preprint]. 2025 Sep 29:2025.09.29.678806. doi: 10.1101/2025.09.29.678806 (opens in new tab). PMID: 41256533 (opens in new tab). PMCID: PMC12621989 (opens in new tab).

Parker TD, Bethlehem RAI, Seidlitz J, White SR, David MCB, Kolanko MA, Bernstock JD, Dorfschmidt L, Bourke N, Gailly de Taurines A, Hain JA, Del Giovane M, Graham NSN, Zimmerman KA, Losty EJF, Schöll M, Srikrishna M, Malhotra PA, Patel MC, Scott G, Alexander-Bloch AF, Bullmore ET, Sharp DJ; Alzheimer’s Disease Neuroimaging Initiative; Frontotemporal Lobar Degeneration Neuroimaging Initiative; Lifespan Brain Chart Consortium. Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration. Alzheimers Res Ther. 2025 Nov 12;17(1):244. doi: 10.1186/s13195-025-01872-x (opens in new tab). PMID: 41225656 (opens in new tab). PMCID: PMC12613731 (opens in new tab).

Rajabli F, Benchek P, Tosto G, Kushch N, Sha J, Bazemore K, Zhu C, Lee WP, Haut J, Hamilton-Nelson KL, Wheeler NR, Zhao Y, Farrell JJ, Grunin MA, Leung YY, Kuksa PP, Li D, da Fonseca EL, Mez JB, Palmer EL, Pillai J, Sherva RM, Song YE, Zhang X, Ikeuchi T, Iqbal T, Pathak O, Valladares O, Reyes-Dumeyer D, Kuzma AB, Abner E, Adams LD, Adams PM, Aguirre A, Albert MS, Albin RL, Allen M, Alvarez L, Apostolova LG, Arnold SE, Asthana S, Atwood CS, Auerbach S, Ayres G, Baldwin CT, Barber RC, Barnes LL, Barral S, Beach TG, Becker JT, Beecham GW, Beekly D, Benitez BA, Bennett D, Bertelson J, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Brewer J, Burke JR, Burns JM, Buxbaum JD, Cairns NJ, Cantwell LB, Cao C, Carlson CS, Carlsson CM, Carney RM, Carrasquillo MM, Chasse S, Chesselet MF, Chin NA, Chui HC, Chung J, Craft S, Crane PK, Cribbs DH, Crocco EA, Cruchaga C, Cuccaro ML, Cullum M, Darby E, Davis B, De Jager PL, DeCarli C, DeToledo J, Dick M, Dickson DW, Dombroski BA, Doody RS, Duara R, Ertekin-Taner N, Evans DA, Faber KM, Fairchild TJ, Fallon KB, Fardo DW, Farlow MR, Fernandez-Hernandez V, Ferris S, Friedland RP, Foroud TM, Frosch MP, Fulton-Howard B, Galasko DR, Gamboa A, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Go RCP, Goate AM, Grabowski TJ, Graff-Radford NR, Green RC, Growdon JH, Hakonarson H, Hall J, Hamilton RL, Harari O, Hardy J, Harrell LE, Head E, Henderson VW, Hernandez M, Hohman T, Honig LS, Huebinger RM, Huentelman MJ, Hulette CM, Hyman BT, Hynan LS, Ibanez L, Jarvik GP, Jayadev S, Jin LW, Johnson K, Johnson L, Kamboh MI, Karydas AM, Katz MJ, Kauwe JS, Kaye JA, Keene CD, Khaleeq A, Kikuchi M, Kim R, Knebl J, Kowall NW, Kramer JH, Kukull WA, LaFerla FM, Lah JJ, Larson EB, Lerner A, Leverenz JB, Levey AI, Lieberman AP, Lipton RB, Logue M, Lopez OL, Lunetta KL, Lyketsos CG, Mains D, Margaret FE, Marson DC, Martin ER, Martiniuk F, Mash DC, Masliah E, Massman P, Masurkar A, McCormick WC, McCurry SM, McDavid AN, McDonough S, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Montine TJ, Monuki ES, Morris JC, Mukherjee S, Myers AJ, Nguyen T, Obisesan T, O'Bryant S, Olichney JM, Ory M, Palmer R, Parisi JE, Paulson HL, Pavlik V, Paydarfar D, Perez V, Peskind E, Petersen RC, Petrovitch H, Pierce A, Polk M, Poon WW, Potter H, Qu L, Quiceno M, Quinn JF, Raj A, Raskind M, Reiman EM, Reisberg B, Reisch JS, Ringman JM, Roberson ED, Rodriguear M, Rogaeva E, Rosen HJ, Rosenberg RN, Royall DR, Sabbagh M, Sadovnick AD, Sager MA, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Slifer SH, Small S, Smith AG, Smith JP, Sonnen JA, Spina S, George-Hyslop PS, Starks TD, Stern RA, Stevens AB, Strittmatter SM, Sultzer D, Swerdlow RH, Tanzi RE, Tilson JL, Trojanowski JQ, Troncoso JC, Tsolaki M, Tsuang DW, Van Deerlin VM, van Eldik LJ, Vance JM, Vardarajan BN, Vassar R, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Whitehead PL, Wijsman EM, Wilhelmsen KC, Williams B, Williamson J, Wilms H, Wingo TS, Wisniewski T, Woltjer RL, Woon M, Wright CB, Wu CK, Younkin SG, Yu CE, Yu L, Zhu X, Kunkle BW, Bush WS, Miyashita A, Byrd GS, Wang LS, Farrer LA, Haines JL, Mayeux R, Pericak-Vance MA, Schellenberg GD, Jun GR, Reitz C, Naj AC; Alzheimer’s Disease Genetics Consortium (ADGC). Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease. Genome Biol. 2025 Jul 17;26(1):210. doi: 10.1186/s13059-025-03564-z (opens in new tab). PMID: 40676597 (opens in new tab). PMCID: PMC12273372 (opens in new tab).

Richardson TE, Kandoi S, Almeida FC, Rohde SK, Marx GA, Canbeldek L, Hiya S, Maldonado-Díaz C, Samanamud J, Clare K, Slocum CC, Kulumani Mahadevan LS, Chiu LY, Farrell K, Crary JF, Daoud EV, White CL 3rd, Espinoza SE, Gonzales MM, Oliveira TG, Walker JM. Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change. Alzheimers Res Ther. 2025 Dec 3;17(1):257. doi: 10.1186/s13195-025-01904-6 (opens in new tab). PMID: 41339920 (opens in new tab). PMCID: PMC12676791 (opens in new tab).