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

Chu C, Wang Y, Ma L, Jin L, Pan Y. Development and validation of a predictive model to forecast the cerebrovascular risk burden in older people using the NACC and ROSMAP dataset. Alzheimers Dement. Chu C, Wang Y, Ma L, Jin L, Pan Y. doi: 10.1002/alz.70543. PMID: 40791103. PMCID: PMC12340427.

Dass D, Dang LT, Xicota L, Krinsky-McHale S, Kannappan B, Brickman AM, Christian BT, Head E, O'Bryant SE, Mapstone M, Handen B, Marder K, Lee JH; Alzheimer Biomarker Consortium – Down syndrome (ABC‐DS). Examination of metabolic syndrome in Down syndrome and association with dementia. Alzheimers Dement. Dass D, Dang LT, Xicota L, Krinsky-McHale S, Kannappan B, Brickman AM, Christian BT, Head E, O'Bryant SE, Mapstone M, Handen B, Marder K, Lee JH; Alzheimer Biomarker Consortium – Down syndrome (ABC‐DS). doi: 10.1002/alz.70799. PMID: 41104603. PMCID: PMC12531894.

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. 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. doi: 10.1002/alz.70398. PMID: 40667715. PMCID: PMC12264832.

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. 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. doi: 10.1002/alz.70810. PMID: 41230793. PMCID: PMC12613078.

Jasodanand VH, Kowshik SS, Puducheri S, Romano MF, Xu L, Au R, Kolachalama VB. AI-driven fusion of multimodal data for Alzheimer's disease biomarker assessment. Nat Commun. Jasodanand VH, Kowshik SS, Puducheri S, Romano MF, Xu L, Au R, Kolachalama VB. doi: 10.1038/s41467-025-62590-4. PMID: 40789853. PMCID: PMC12339743.

Andrews EJ, Ngo PT, Pascual JR, Gonzalez F, Phelan M, Wright ST, Harp J, Schmitt F, Lai F, Lao PJ, Brickman AM, Kofler J, Ikonomovic MD, Head E; ABC‐DS Consortium. Age and sex are associated with Alzheimer's disease neuropathology in Down syndrome. Alzheimers Dement. Andrews EJ, Ngo PT, Pascual JR, Gonzalez F, Phelan M, Wright ST, Harp J, Schmitt F, Lai F, Lao PJ, Brickman AM, Kofler J, Ikonomovic MD, Head E; ABC‐DS Consortium. doi: 10.1002/alz.70408. PMID: 40673442. PMCID: PMC12268376.

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. 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. doi: 10.1002/alz.70358. PMID: 40667702. PMCID: PMC12265027.

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. 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. doi: 10.1186/s12974-025-03607-z. PMID: 41388301. PMCID: PMC12781401.

Cai M, Lei H, Zhang Y, Zou J, Cao W, Wang Y, Wei K. APOE ε4 -Associated Hippocampal Atrophy Trajectories Across the Alzheimer's Disease Continuum: A Systematic Review, Meta-Analysis, and Longitudinal Validation. medRxiv [Preprint]. Cai M, Lei H, Zhang Y, Zou J, Cao W, Wang Y, Wei K. doi: 10.64898/2025.12.08.25341534. PMID: 41409668. PMCID: PMC12706602.

Martinez N, Bharani KL, Hasan S, Hayes CA. Micro infarcts are associated with cognitive impairment in neurofibrillary tangle predominant decedents: evidence from the NACC autopsy cohort. Alzheimers ResTher. Martinez N, Bharani KL, Hasan S, Hayes CA. doi: 10.1186/s13195-025-01863-y. PMID: 41035071. PMCID: PMC12486553.

Pirraglia E, Osorio RS, Glodzik L, Ashebir Y, Shao Y. Subtypes of multiple-etiology dementias and the heterogeneous impact of APOE variants. Alzheimers Dement. Pirraglia E, Osorio RS, Glodzik L, Ashebir Y, Shao Y. doi: 10.1002/alz.70872. PMID: 41198610. PMCID: PMC12591992.

Perez SE, Miguel JC, Nadeem M, Malek-Ahmadi M, Hales CM, Head E, Mufson EJ. U1-70K and U1A and taupathogenesis in demented and non-demented individuals with Down syndrome. Alzheimers Dement. Perez SE, Miguel JC, Nadeem M, Malek-Ahmadi M, Hales CM, Head E, Mufson EJ. doi: 10.1002/alz.70474. PMID: 40762109. PMCID: PMC12322699.

Piras IS, Bonfitto A, Song S, Aldabergenova A, Sloan J, Trejo A, Troncoso JC, Geula C, Rogalski EJ, Kawas CH, Corrada M, Beach TG, Serrano GE, Worley PF, Barnes CA, Huentelman MJ. Transcriptomic profiling of the middle temporal gyrus reveals differential glial/neuronal dysregulation across Alzheimer's disease and aging. bioRxiv [Preprint]. Piras IS, Bonfitto A, Song S, Aldabergenova A, Sloan J, Trejo A, Troncoso JC, Geula C, Rogalski EJ, Kawas CH, Corrada M, Beach TG, Serrano GE, Worley PF, Barnes CA, Huentelman MJ. doi: 10.1101/2025.10.19.683343. PMID: 41278792. PMCID: PMC12633431.

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. 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. doi: 10.1186/s13195-025-01904-6. PMID: 41339920. PMCID: PMC12676791.

Sordo L, Du A, Sandadi V, Dustagheer FB, Pascual J, Ngo P, Hom CL, Doran E, Head E. Leptin levels are associated with body mass index and Alzheimer's disease in Down syndrome. Alzheimers Dement. Sordo L, Du A, Sandadi V, Dustagheer FB, Pascual J, Ngo P, Hom CL, Doran E, Head E. doi: 10.1002/alz.70448. PMID: 40635163. PMCID: PMC12240871.

Tang C, Yang J, Lei X, Zhang M, Chen Y, Peng X, He D. Unraveling the complexity of neurodegeneration: heterogeneous damage patterns of locus coeruleus and substantia nigra in Alzheimer's disease. Alzheimers Dement. Tang C, Yang J, Lei X, Zhang M, Chen Y, Peng X, He D. doi: 10.1002/alz.70605. PMID: 40891260. PMCID: PMC12402704.

Wood Alexander M, Fischer DL, VandeVrede L, Nichols E, Yu L, Pike JR, Swardfager W, Wu CY, Masellis M, Galea LAM, Zukotynski K, Einstein G, Black SE, Barnes LL, Schneider JA, Arvanitakis Z, Casaletto KB, Rabin JS. Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline. Ann Neurol. Wood Alexander M, Fischer DL, VandeVrede L, Nichols E, Yu L, Pike JR, Swardfager W, Wu CY, Masellis M, Galea LAM, Zukotynski K, Einstein G, Black SE, Barnes LL, Schneider JA, Arvanitakis Z, Casaletto KB, Rabin JS. doi: 10.1002/ana.27308. PMID: 40646704. PMCID: PMC12341763.

Zhao R, Sophanpanichkul P, Chadarevian JP, Ding Y, Dai H, Nayak M, Davtyan H, Blurton-Jones M, Goldstein SAN. Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release. Proc Natl Acad Sci U S A. Zhao R, Sophanpanichkul P, Chadarevian JP, Ding Y, Dai H, Nayak M, Davtyan H, Blurton-Jones M, Goldstein SAN. doi: 10.1073/pnas.2509903122. PMID: 41129234. PMCID: PMC12582281.