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Cited by 19Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid-β predominant Alzheimer’s disease neuropathologic change

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Kovacs, Gabor G, Katsumata, Yuriko, Wu, Xian, Aung, Khine Zin, Fardo, David W, Forrest, Shelley L, Alzheimer's Disease Genetics Consortium, Bowen, James D +213 more·2025·Brain
DOI 10.1093/brain/awae325PMC PMC11788189
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Abstract

Different subsets of Alzheimer’s disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer’s Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies.

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  • Alzheimer's disease is characterized by neuritic plaques and neurofibrillary tangles resulting from amyloid-beta accumulation, aggregation of fibrillar plaques, and hyperphosphorylation of tau protein.

    “Previous studies of AD pathology have demonstrated that the disease is characterized by the presence of neuritic plaques and neurofibrillary tangles resulting from amyloid-beta (Aβ) accumulation, aggregation of fibrillar plaques, and hyperphosphorylation of tau protein (Depp et al., 2023; Zhang et al., 2023; Kovacs et al., 2024; Wang et al., 2024; Zhang et al., 2025).”

    From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kovacs et al., 2024

    The Introduction (page unavailable) says AD neuropathologic change is classically characterized by amyloid-β and tau pathologies, including neurofibrillary tangles; the Discussion also mentions neuritic plaques. The paper does not establish the claim’s more specific account of fibrillar-plaque aggregation and tau hyperphosphorylation producing those lesions, and it describes cases with extensive amyloid deposition but little tau pathology. (LLM, conf=0.84)

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Authors
Kovacs, G. G., Katsumata, Y., Wu, X., Aung, K. Z., Fardo, D. W., Forrest, S. L., Alzheimer's Disease Genetics Consortium, Bowen, J. D., Crane, P. K., Jarvik, G. P., Keene, C. D., Larson, E. B., McCormick, W. C., McCurry, S. M., Mukherjee, S., Kowall, N. W., McKee, A. C., Stern, R. A., Baldwin, C. T., Farrer, L. A., Jun, G., Lunetta, K. L., Honig, L. S., Vonsattel, J. P., Williamson, J., Small, S., Barral, S., Reitz, C., Vardarajan, B. N., Mayeux, R., Burke, J. R., Hulette, C. M., Welsh-Bohmer, K. A., Gearing, M., Lah, J. J., Levey, A. I., Wingo, T. S., Apostolova, L. G., Farlow, M. R., Ghetti, B., Saykin, A. J., Spina, S., Faber, K. M., Foroud, T. M., Albert, M. S., Lyketsos, C. G., Troncoso, J. C., Frosch, M. P., Green, R. C., Growdon, J. H., Hyman, B. T., Tanzi, R. E., Potter, H., Dickson, D. W., Ertekin-Taner, N., Graff-Radford, N. R., Parisi, J. E., Petersen, R. C., Boeve, B. F., Allen, M., Carrasquillo, M. M., Younkin, S. G., Duara, R., Buxbaum, J. D., Goate, A. M., Sano, M., Masurkar, A. V., Wisniewski, T., Bigio, E. H., Mesulam, M., Weintraub, S., Vassar, R., Kaye, J. A., Quinn, J. F., Woltjer, R. L., Barnes, L. L., Yu, L., Evans, D. A., Henderson, V., Fallon, K. B., Harrell, L. E., Marson, D. C., Roberson, E. D., DeCarli, C., Jin, L.-W., Olichney, J. M., Kim, R., LaFerla, F. M., Monuki, E., Head, E., Sultzer, D., Geschwind, D. H., Vinters, H. V., Chesselet, M.-F., Galasko, D. R., Brewer, J. B., Boxer, A., Karydas, A., Kramer, J. H., Miller, B. L., Rosen, H. J., Seeley, W. W., Burns, J. M., Swerdlow, R. H., Van Eldik, L. J., Albin, R. L., Lieberman, A. P., Paulson, H. L., Arnold, S. E., Trojanowski, J. Q., Van Deerlin, V. M., Cantwell, L. B., Kuzma, A. P., Malamon, J., Naj, A. C., Qu, L., Schellenberg, G. D., Valladares, O., Wang, L.-S., Zhao, Y., Hamilton, R. L., Kamboh, M. I., Lopez, O. L., Becker, J. T., Cao, C., Raj, A., Smith, A. G., Chui, H. C., Miller, C. A., Ringman, J. M., Schneider, L. S., Bird, T. D., Sonnen, J. A., Yu, C.-E., Grabowsk, T., Peskind, E., Raskind, M., Li, G., Tsuang, D. W., Asthana, S., Atwood, C. S., Carlsson, C. M., Sager, M. A., Chin, N. A., Craft, S., Cairns, N. J., Morris, J. C., Cruchaga, C., Strittmatter, S., Reiman, E. M., Beach, T. G., Huentelman, M. J., Hardy, J., Kauwe, J. S. K., Hakonarson, H., Blacker, D., Montine, T. J., Bush, W. S., Haines, J. L., Lerner, A. J., Zhou, X., Beecham, G. W., Carney, R. M., Cuccaro, M. L., Gilbert, J. R., Hamilton-Nelson, K. L., Kunkle, B. W., Martin, E. R., Pericak-Vance, M. A., Vance, J. M., Myers, A. J., Leverenz, J. B., De Jager, P. L., Katz, M. J., Lipton, R. B., Pavlik, V., Massman, P., Darby, E., Rodriguear, M., Khaleeq, A., Royall, D. R., Stevens, A., Ory, M., DeToledo, J. C., Wilms, H., Johnson, K., Perez, V., Hernandez, M., Wilhelmsen, K. C., Tilson, J., Chasse, S., Barber, R. C., Fairchild, T. J., O’Bryant, S. E., Knebl, J., Hall, J. R., Johnson, L., Mains, D., Alvarez, L., Gamboa, A., Paydarfar, D., Bertelson, J., Woon, M., Ayres, G., Aguirre, A., Palmer, R., Polk, M., Adams, P. M., Huebinger, R. M., Reisch, J. S., Rosenberg, R. N., Cullum, M., Williams, B., Quiceno, M., Hynan, L., Smith, J., Davis, B., Nguyen, T., Rogaeva, E., George-Hyslop, P. S., & Nelson, P. T.
Affiliations
  • Tanz Centre for Research in Neurodegenerative Disease and Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario M5T 0S8 ,
  • University of Kentucky (US)
  • University Health Network (CA)
Corresponding author
Nelson, Peter T
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2024-10-17
Volume
148
Issue
2
Pages
401-407
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awae325
PMC
PMC11788189
OpenAlex
W4403479144
Cited by
19
References
5
Citations by year
2026: 11 · 2025: 8
FWCI
5.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (1U24NS133945-01, P30 AG072946, R01 AG061111, RF1 NS118584, R01 AG057187)
  • National Institute on Aging (U01 AG032984, RC2 AG036528)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid plaques, tau tangles, genetic polymorphism, apolipoprotein E, SNX1, Wnt3, MAPT, immunoglobulin heavy chain, clinical features, National Alzheimer's Coordinating Center
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Brain, Female, Humans, Male, Middle Aged, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Tauopathies, Plaque, Amyloid, Sorting Nexins

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