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

D. Luke Fischer; Lea T. Grinberg; Jared T. Ahrendsen; Thomas G. Beach; Kevin F. Bieniek; Rudolph J. Castellani; Rati Chkheidze; Inma Cobos; Mark Cohen; John F. Crary; Dennis W. Dickson; Brittany N. Dugger; Sara R. Dunlop; Kurt Farrell; Bernardino Ghetti; Mohammad Haeri; William Harrison; Elizabeth Head; Annie Hiniker; Eric J. Huang; Anita Huttner; Pouya Jamshidi; Alifiya Kapasi; C. Dirk Keene; Julia Kofler; Caitlin S. Latimer; Ann C. McKee; Karin Mente; Michael B. Miller; Thomas J. Montine; Meaghan Morris; Melissa E. Murray; Peter T. Nelson; Kathy L. Newell; Richard J. Perrin; Biswarathan Ramani; R. Ross Reichard; Subhojit Roy; Johannes C.M. Schlachetzki; William W. Seeley; Geidy E. Serrano; Salvatore Spina; Andrew F. Teich; Shih Hsiu J. Wang; Thomas Wisniewski; Edward B. Lee

doi:10.1002/alz.70734

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

D. Luke Fischer
, Lea T. Grinberg
, Jared T. Ahrendsen
, Thomas G. Beach
, Kevin F. Bieniek
, Rudolph J. Castellani
, Rati Chkheidze
, Inma Cobos
, Mark Cohen
, John F. Crary
, Dennis W. Dickson
, Brittany N. Dugger
, Sara R. Dunlop
, Kurt Farrell
, Bernardino Ghetti
, Mohammad Haeri
, William Harrison
, Elizabeth Head
, Annie Hiniker
, Eric J. Huang

Anita Huttner, Pouya Jamshidi, Alifiya Kapasi, C. Dirk Keene, Julia Kofler, Caitlin S. Latimer, Ann C. McKee, Karin Mente, Michael B. Miller, Thomas J. Montine, Meaghan Morris, Melissa E. Murray, Peter T. Nelson, Kathy L. Newell, Richard J. Perrin, Biswarathan Ramani, R. Ross Reichard, Subhojit Roy, Johannes C.M. Schlachetzki, William W. Seeley, Geidy E. Serrano, Salvatore Spina, Andrew F. Teich, Shih Hsiu J. Wang, Thomas Wisniewski, Edward B. Lee

Producción científica: Comment/debate

4 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	e70734
Publicación	Alzheimer's and Dementia
Volumen	21
N.º	10
DOI	https://doi.org/10.1002/alz.70734
Estado	Published - oct 2025

Nota bibliográfica

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Financiación

The authors acknowledge the invaluable contributions of the study participants and families as well as the assistance of the support staffs at each of the participating sites of the ADRC network and the NACC. The authors also acknowledge the past luminaries in neuropathology, who are no longer with us, and they acknowledge the NIA, especially Dr. Cerise Elliott, Dr. Zaven Khachaturian, Dr. Creighton “Tony” Phelps, and Dr. Nina Silverberg. D.L.F. is supported by NIH grant UE5NS070680 and the Alzheimer's Association with the Fred and Barbara Erb Family Foundation. L.T.G, S.R.D., B.G., M.E.M, and K.L.N. are supported by NIH grant R01 AG075802. B.G. and K.L.N. are supported by NIH grant P30 AG072976. T.G.B. is supported by NIH grants P30AG019610 and P30AG072980. R.J.C. and P.J. are supported by NIH grant P30AG072977. I.C. is supported by NIH grant P30AG066515. J.F.C. is supported by NIH grants P30AG066514, R01AG054008, R01NS095252, and R01AG062348, as well as 10,000 Brains NeuroAI Inc., the Rainwater Charitable Trust /Tau Consortium, the Karen Strauss Cook Research Scholar Award, and a generous gift from Stuart Katz and Dr. Jane Martin. D.W.D, M.E.M, and R.R.R. are supported by NIH grant P30AG062677. D.W.D. and M.E.M. are supported by Rainwater Charitable Trust and Alzheimer's Association Florida Gulf Coast Chapter SG-25-1416824. B.N.D. is supported by NIH grants R01AG062517, U24NS133949, P30AG072972, and additional support from the Chan Zuckerberg Initiative DAF (2024-351073) and an advised fund of the Silicon Valley Community Foundation. K.F. is supported by NIH grant K01 AG070326 and the CurePSP 685-2023-06-Pathway grant. E.J.H. is supported by NIH grant RF1NS128908. A.H. is supported by NIH grant P30AG066508. W.H. is supported by NIH grants P30AG072947 and R24AG073199. C.D.K. is supported by NIH grants P30AG066509, P30AG072947, P30AG062715, U19AG066567, U19AG060909, UM1MH130981, UM1MH134812, U24AG072458, U24NS133949; U24NS133945, U24NS135651, R24AG073137, U01NS137500, U01NS137484, U01AG082350, R01AG082730, R01AG087226, R01AG088656, R01AG060942, R01AG080585, and R01NS129609, DoD W81XWH-21-S-TBIPH2, the Allen Institute for Brain Science, and the Nancy and Buster Alvord Endowment. J.K. is supported by NIH grants R01AG069912, P30AG066468, U19AG068054, R01MH116046, and U01NS137500. C.L. is supported by NIH grants P30AG066509 and R01AG090551. K.M. is supported by NIH grant P30AG072959. M.B.M. is supported by NIH grants DP2AG086138 and R01AG082346. M.M. is supported by NIH grant P30AG066507. R.J.P. is supported by NIH grants P01AG003991, P30AG066444, U19AG024904, U19AG032438, R01AG068319, and R01AG053267. S.R. is supported by NIH grants R01NS111978 and UF1NS120463. W.W.S. is supported by NIH grants AG023501, AG019724, AG057195, and AG063911; the Rainwater Charitable Foundation; and the Bluefield Project to Cure FTD. S.-H.W. is supported by NIH grant P30AG072958. T.W. is supported by NIH grants P30AG066512, R01AG077422, U01OH012486, U24NS135568 and R01AG087280. E.B.L. is supported by NIH grants R13AG059336, P30AG072979, P01AG066597, P01AG084497, RF1AG065341, U01NS137500, the DeCrane Family Fund for PPA Research, and by gifts from the Shanahan Family Foundation and the Barrist Family Foundation. The NACC database is funded by NIA/NIH grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI David Holtzman, MD), P30 AG066518 (PI Lisa Silbert, MD, MCR), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI Julie A. Schneider, MD, MS), P30 AG072978 (PI Ann McKee, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Jessica Langbaum, PhD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Glenn Smith, PhD, ABPP), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P30 AG086401 (PI Erik Roberson, MD, PhD), P30 AG086404 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). The NACC database is funded by NIA/NIH grant U24 AG072122. NACC data are contributed by the NIA‐funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI David Holtzman, MD), P30 AG066518 (PI Lisa Silbert, MD, MCR), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI Julie A. Schneider, MD, MS), P30 AG072978 (PI Ann McKee, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Jessica Langbaum, PhD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Glenn Smith, PhD, ABPP), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P30 AG086401 (PI Erik Roberson, MD, PhD), P30 AG086404 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). The authors acknowledge the invaluable contributions of the study participants and families as well as the assistance of the support staffs at each of the participating sites of the ADRC network and the NACC. The authors also acknowledge the past luminaries in neuropathology, who are no longer with us, and they acknowledge the NIA, especially Dr. Cerise Elliott, Dr. Zaven Khachaturian, Dr. Creighton “Tony” Phelps, and Dr. Nina Silverberg. D.L.F. is supported by NIH grant UE5NS070680 and the Alzheimer's Association with the Fred and Barbara Erb Family Foundation. L.T.G, S.R.D., B.G., M.E.M, and K.L.N. are supported by NIH grant R01 AG075802. B.G. and K.L.N. are supported by NIH grant P30 AG072976. T.G.B. is supported by NIH grants P30AG019610 and P30AG072980. R.J.C. and P.J. are supported by NIH grant P30AG072977. I.C. is supported by NIH grant P30AG066515. J.F.C. is supported by NIH grants P30AG066514, R01AG054008, R01NS095252, and R01AG062348, as well as 10,000 Brains NeuroAI Inc., the Rainwater Charitable Trust /Tau Consortium, the Karen Strauss Cook Research Scholar Award, and a generous gift from Stuart Katz and Dr. Jane Martin. D.W.D, M.E.M, and R.R.R. are supported by NIH grant P30AG062677. D.W.D. and M.E.M. are supported by Rainwater Charitable Trust and Alzheimer's Association Florida Gulf Coast Chapter SG‐25‐1416824. B.N.D. is supported by NIH grants R01AG062517, U24NS133949, P30AG072972, and additional support from the Chan Zuckerberg Initiative DAF (2024‐351073) and an advised fund of the Silicon Valley Community Foundation. K.F. is supported by NIH grant K01 AG070326 and the CurePSP 685‐2023‐06‐Pathway grant. E.J.H. is supported by NIH grant RF1NS128908. A.H. is supported by NIH grant P30AG066508. W.H. is supported by NIH grants P30AG072947 and R24AG073199. C.D.K. is supported by NIH grants P30AG066509, P30AG072947, P30AG062715, U19AG066567, U19AG060909, UM1MH130981, UM1MH134812, U24AG072458, U24NS133949; U24NS133945, U24NS135651, R24AG073137, U01NS137500, U01NS137484, U01AG082350, R01AG082730, R01AG087226, R01AG088656, R01AG060942, R01AG080585, and R01NS129609, DoD W81XWH‐21‐S‐TBIPH2, the Allen Institute for Brain Science, and the Nancy and Buster Alvord Endowment. J.K. is supported by NIH grants R01AG069912, P30AG066468, U19AG068054, R01MH116046, and U01NS137500. C.L. is supported by NIH grants P30AG066509 and R01AG090551. K.M. is supported by NIH grant P30AG072959. M.B.M. is supported by NIH grants DP2AG086138 and R01AG082346. M.M. is supported by NIH grant P30AG066507. R.J.P. is supported by NIH grants P01AG003991, P30AG066444, U19AG024904, U19AG032438, R01AG068319, and R01AG053267. S.R. is supported by NIH grants R01NS111978 and UF1NS120463. W.W.S. is supported by NIH grants AG023501, AG019724, AG057195, and AG063911; the Rainwater Charitable Foundation; and the Bluefield Project to Cure FTD. S.‐H.W. is supported by NIH grant P30AG072958. T.W. is supported by NIH grants P30AG066512, R01AG077422, U01OH012486, U24NS135568 and R01AG087280. E.B.L. is supported by NIH grants R13AG059336, P30AG072979, P01AG066597, P01AG084497, RF1AG065341, U01NS137500, the DeCrane Family Fund for PPA Research, and by gifts from the Shanahan Family Foundation and the Barrist Family Foundation.

Financiadores	Número del financiador
Alzheimer's Disease Research Center, University of Pittsburgh
Shanahan Family Foundation
CurePSP Foundation
Institut des Sciences du Cerveau de Toulouse
NIA
National Alzheimer's Coordinating Center
U.S. Department of Health & Human Services \| NIH \| National Institute on Aging (U.S. National Institute on Aging)
Alzheimer's Association	SG-25-1416824
Silicon Valley Community Foundation	U19AG060909, U01NS137484, RF1NS128908, UM1MH134812, UM1MH130981, R01NS129609, U24NS135651, U01AG082350, P30AG062715, R24AG073137, P30AG066509, P30AG066508, U01NS137500, R24AG073199, U19AG066567, U24AG072458, U24NS133945, P30AG072947, R01AG082730, R01AG060942, R01AG080585, R01AG087226, K01 AG070326, R01AG088656
Nancy and Buster Alvord Endowment	R01AG068319, R01AG069912, AG023501, R01NS111978, R01AG090551, U19AG024904, R01MH116046, R01AG053267, P30AG066507, AG063911, UF1NS120463, AG057195, P30AG066468, P01AG003991, P30AG066444, P30AG072959, DP2AG086138, AG019724, U19AG068054, U19AG032438, R01AG082346
Rainwater Charitable Foundation	P01AG066597, R01AG077422, U24NS135568, RF1AG065341, P30AG066512, P30AG072958, R01AG087280, R13AG059336, U01OH012486, P01AG084497, P30AG072979
Barrist Family Foundation	P30 AG086401, P30 AG079280, P30 AG062421, P30 AG086404, P30 AG062422, P30 AG066546, P30 AG066506, P30 AG066518, P30 AG062429, P30 AG066519, P30 AG072975, P30 AG066462, P30 AG072931, P30 AG066530, P20 AG068082, P30 AG066511, P30 AG072973, U24 AG072122, P30 AG072978, P30 AG072946
National Institutes of Health (NIH)	UE5NS070680, U24 AG072122
Chan Zuckerberg Initiative	2024‐351073
Rainwater Charitable Trust	P30AG072972, P30AG062677, R01AG062517, U24NS133949
Fred A. And Barbara M. Erb Family Foundation	R01AG054008, P30 AG072976, P30AG066515, P30AG066514, P30AG072980, P30AG019610, R01 AG075802, R01AG062348, P30AG072977, R01NS095252
U.S. Department of Defense	W81XWH‐21‐S‐TBIPH2

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.70734

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Fischer, D. L., Grinberg, L. T., Ahrendsen, J. T., Beach, T. G., Bieniek, K. F., Castellani, R. J., Chkheidze, R., Cobos, I., Cohen, M., Crary, J. F., Dickson, D. W., Dugger, B. N., Dunlop, S. R., Farrell, K., Ghetti, B., Haeri, M., Harrison, W., Head, E., Hiniker, A., ... Lee, E. B. (2025). Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers. Alzheimer's and Dementia, 21(10), Artículo e70734. https://doi.org/10.1002/alz.70734

@article{491273d1a9bf4cb29ece9d8b557f1b58,

title = "Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers",

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",

author = "Fischer, \{D. Luke\} and Grinberg, \{Lea T.\} and Ahrendsen, \{Jared T.\} and Beach, \{Thomas G.\} and Bieniek, \{Kevin F.\} and Castellani, \{Rudolph J.\} and Rati Chkheidze and Inma Cobos and Mark Cohen and Crary, \{John F.\} and Dickson, \{Dennis W.\} and Dugger, \{Brittany N.\} and Dunlop, \{Sara R.\} and Kurt Farrell and Bernardino Ghetti and Mohammad Haeri and William Harrison and Elizabeth Head and Annie Hiniker and Huang, \{Eric J.\} and Anita Huttner and Pouya Jamshidi and Alifiya Kapasi and Keene, \{C. Dirk\} and Julia Kofler and Latimer, \{Caitlin S.\} and McKee, \{Ann C.\} and Karin Mente and Miller, \{Michael B.\} and Montine, \{Thomas J.\} and Meaghan Morris and Murray, \{Melissa E.\} and Nelson, \{Peter T.\} and Newell, \{Kathy L.\} and Perrin, \{Richard J.\} and Biswarathan Ramani and Reichard, \{R. Ross\} and Subhojit Roy and Schlachetzki, \{Johannes C.M.\} and Seeley, \{William W.\} and Serrano, \{Geidy E.\} and Salvatore Spina and Teich, \{Andrew F.\} and Wang, \{Shih Hsiu J.\} and Thomas Wisniewski and Lee, \{Edward B.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = oct,

doi = "10.1002/alz.70734",

language = "English",

volume = "21",

number = "10",

}

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, SHJ, Wisniewski, T & Lee, EB 2025, 'Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers', Alzheimer's and Dementia, vol. 21, n.º 10, e70734. https://doi.org/10.1002/alz.70734

TY - JOUR

T1 - Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

AU - Fischer, D. Luke

AU - Grinberg, Lea T.

AU - Ahrendsen, Jared T.

AU - Beach, Thomas G.

AU - Bieniek, Kevin F.

AU - Castellani, Rudolph J.

AU - Chkheidze, Rati

AU - Cobos, Inma

AU - Cohen, Mark

AU - Crary, John F.

AU - Dickson, Dennis W.

AU - Dugger, Brittany N.

AU - Dunlop, Sara R.

AU - Farrell, Kurt

AU - Ghetti, Bernardino

AU - Haeri, Mohammad

AU - Harrison, William

AU - Head, Elizabeth

AU - Hiniker, Annie

AU - Huang, Eric J.

AU - Huttner, Anita

AU - Jamshidi, Pouya

AU - Kapasi, Alifiya

AU - Keene, C. Dirk

AU - Kofler, Julia

AU - Latimer, Caitlin S.

AU - McKee, Ann C.

AU - Mente, Karin

AU - Miller, Michael B.

AU - Montine, Thomas J.

AU - Morris, Meaghan

AU - Murray, Melissa E.

AU - Nelson, Peter T.

AU - Newell, Kathy L.

AU - Perrin, Richard J.

AU - Ramani, Biswarathan

AU - Reichard, R. Ross

AU - Roy, Subhojit

AU - Schlachetzki, Johannes C.M.

AU - Seeley, William W.

AU - Serrano, Geidy E.

AU - Spina, Salvatore

AU - Teich, Andrew F.

AU - Wang, Shih Hsiu J.

AU - Wisniewski, Thomas

AU - Lee, Edward B.

PY - 2025/10

Y1 - 2025/10

N2 - 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.

AB - 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.

KW - Alzheimer disease

KW - dementia

KW - neurodegenerative diseases

KW - neuropathology

KW - pathomics

UR - https://www.scopus.com/pages/publications/105018647840

UR - https://www.scopus.com/pages/publications/105018647840#tab=citedBy

U2 - 10.1002/alz.70734

DO - 10.1002/alz.70734

M3 - Comment/debate

C2 - 41085158

AN - SCOPUS:105018647840

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 10

M1 - e70734

ER -

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

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