Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

D Luke Fischer¹, Lea T Grinberg^{2

3

4}, Jared T Ahrendsen⁵, Thomas G Beach⁶, Kevin F Bieniek⁷, Rudolph J Castellani^{5

8}, Rati Chkheidze⁹, Inma Cobos¹⁰, Mark Cohen¹¹, John F Crary¹², Dennis W Dickson^{2

3}, Brittany N Dugger¹³, Sara R Dunlop³, Kurt Farrell¹², Bernardino Ghetti¹⁴, Mohammad Haeri¹⁵, William Harrison¹⁶, Elizabeth Head¹⁷, Annie Hiniker¹⁸, Eric J Huang¹⁹, Anita Huttner²⁰, Pouya Jamshidi^{5

8}, Alifiya Kapasi²¹, C Dirk Keene²², Julia Kofler²³, Caitlin S Latimer²², Ann C McKee²⁴, Karin Mente^{11

25}, Michael B Miller²⁶, Thomas J Montine¹⁰, Meaghan Morris²⁷, Melissa E Murray^{2

3}, Peter T Nelson²⁸, Kathy L Newell¹⁴, Richard J Perrin^{19

29}, Biswarathan Ramani³⁰, R Ross Reichard³¹, Subhojit Roy^{32

33}, Johannes C M Schlachetzki³², William W Seeley^{1

30}, Geidy E Serrano⁶, Salvatore Spina¹, Andrew F Teich³⁴, Shih-Hsiu J Wang³⁵, Thomas Wisniewski³⁶, Edward B Lee³⁷

Affiliations

¹ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
³ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
⁴ Department of Pathology, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
⁵ Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁶ Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
⁷ Department of Pathology and Laboratory Medicine, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
⁸ Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁹ Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
¹¹ Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
¹² Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, California, USA.
¹⁴ Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁵ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹⁶ Department of Pathology, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, North Carolina, USA.
¹⁷ Department of Pathology and Laboratory Medicine, University of California Irvine, 1111 Gillespie Neuroscience Research Facility, Irvine, California, USA.
¹⁸ Department of Pathology, University of Southern California, Los Angeles, California, USA.
¹⁹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
²⁰ Department of Pathology, Yale University, New Haven, Connecticut, USA.
²¹ Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
²² Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
²³ Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
²⁴ Departments of Neurology and Pathology and Laboratory Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts, USA.
²⁵ Department of Neurology, Case Western Reserve University and Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
²⁶ Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
²⁷ Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
²⁸ Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky, USA.
²⁹ Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁰ Department of Pathology, University of California San Francisco, San Francisco, California, USA.
³¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
³² Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
³³ Department of Pathology, University of California San Diego, La Jolla, California, USA.
³⁴ Department of Pathology and Cell Biology and Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA.
³⁵ Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
³⁶ Center for Cognitive Neurology, Departments of Pathology, Neurology, and Psychiatry, New York University Grossman School of Medicine, New York, New York, USA.
³⁷ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 41085158
PMCID: PMC12519528
DOI: 10.1002/alz.70734

Review

Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

D Luke Fischer et al. Alzheimers Dement. 2025 Oct.

. 2025 Oct;21(10):e70734.

doi: 10.1002/alz.70734.

Authors

Affiliations

¹ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
³ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
⁴ Department of Pathology, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
⁵ Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁶ Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
⁷ Department of Pathology and Laboratory Medicine, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
⁸ Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁹ Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
¹¹ Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
¹² Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, California, USA.
¹⁴ Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁵ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹⁶ Department of Pathology, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, North Carolina, USA.
¹⁷ Department of Pathology and Laboratory Medicine, University of California Irvine, 1111 Gillespie Neuroscience Research Facility, Irvine, California, USA.
¹⁸ Department of Pathology, University of Southern California, Los Angeles, California, USA.
¹⁹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
²⁰ Department of Pathology, Yale University, New Haven, Connecticut, USA.
²¹ Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
²² Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
²³ Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
²⁴ Departments of Neurology and Pathology and Laboratory Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts, USA.
²⁵ Department of Neurology, Case Western Reserve University and Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
²⁶ Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
²⁷ Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
²⁸ Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky, USA.
²⁹ Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁰ Department of Pathology, University of California San Francisco, San Francisco, California, USA.
³¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
³² Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
³³ Department of Pathology, University of California San Diego, La Jolla, California, USA.
³⁴ Department of Pathology and Cell Biology and Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA.
³⁵ Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
³⁶ Center for Cognitive Neurology, Departments of Pathology, Neurology, and Psychiatry, New York University Grossman School of Medicine, New York, New York, USA.
³⁷ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 41085158
PMCID: PMC12519528
DOI: 10.1002/alz.70734

Abstract

Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical-pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease-modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences. HIGHLIGHTS: We celebrate 40 years of NIA-funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD. Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies. Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease-modifying therapies. Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics. Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.

Keywords: Alzheimer disease; dementia; neurodegenerative diseases; neuropathology; pathomics.

PubMed Disclaimer

Conflict of interest statement

D.L.F. has received authorship payment from MedLink, LLC and an honorarium from Topline Bio. K.M. has received consulting fees from Spear Bio. E.B.L. has received consulting fees from Eli Lilly and Wavebreak Therapeutics. Other author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
NACC neuropathology data since inception. The number of participants in the NACC dataset with neuropathology forms was queried as of June 2025 data freeze and plotted since NACC's inception (analysis using R and graphed with Prism) through only 2023, due to the delay from the time required to process tissue, analyze results, and submit data to the NACC. The number of autopsies performed at ADRCs has remained relatively constant over two decades, maintaining linear growth of the total number of cases over time. NACC, National Alzheimer's Coordinating Center.

See this image and copyright information in PMC

References

1. Beach TG. A history of senile plaques: from Alzheimer to amyloid imaging. J Neuropathol Exp Neurol. 2022;81:387‐413. - PMC - PubMed
1. Goedert M. Oskar Fischer and the study of dementia. Brain. 2009;132:1102‐1111. - PMC - PubMed
1. Katzman R. Editorial: the prevalence and malignancy of Alzheimer disease. a major killer. Arch Neurol. 1976;33:217‐218. - PubMed
1. Brion J‐P, Passareiro H, Nunez J, Flament‐Durand J. Immunological demonstration of tau protein into neurofibrillary tangles of Alzheimer's disease. Arch Biol (Bruxelles). 1985;95:229‐235.
1. Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci USA. 1975;72:1858‐1862. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- PubMed Central
- Wiley
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

Affiliations

Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical