The DOI matches its Crossref record; 280 of the 281 references it cites were found in a registry or an index.
“New Old Pathologies”: AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS)
Open accessAbstract
The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD "mimic," which has been termed "hippocampal sclerosis of aging" or "hippocampal sclerosis dementia." This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pathogenetic influences contribute to TDP-43 pathology and hippocampal sclerosis. Because hippocampal sclerosis of aging affects the "oldest-old" with arteriolosclerosis and TDP-43 pathologies that extend well beyond the hippocampus, more appropriate terminology for this disease is required. We recommend "cerebral age-related TDP-43 and sclerosis" (CARTS). A detailed case report is presented, which includes neuroimaging and longitudinal neurocognitive data. Finally, we suggest a neuropathology-based diagnostic rubric for CARTS.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As the distribution of TDP-43 increases from limbic regions to other parts of the brain, it is associated with worsening cognition and with medial temporal atrophy on antemortem brain imaging [130, 132, 133].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
In the citing paper
“Primary age-related tauopathy (PART) and aging-related tau astrogliopathy (ARTAG) are independent tau pathologies commonly observed in patients over 80 years of age, and PART may account for a proportion of the misdiagnosed clinical AD cases in the elderly [130, 141, 142].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
In the citing paper
“Hippocampal sclerosis of aging is now recognized to almost always include TDP-43 deposits and sometimes arteriolosclerosis that lead to intracellular and neuritic deposits of TDP-43 in the hippocampus during the preclinical state and eventually hippocampal sclerosis and cerebral atrophy in the disease state [130, 131].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
In the citing paper
“Lesions are found in the hippocampus and adjacent regions similar to those observed in Braak I-IV, but PART is distinct from AD in that it lacks amyloid plaques, and it has distinct morbidity and age range [130, 142].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
In the citing paper
“ARTAG represents astrocytic tau pathology distinct from that observed in primary tauopathies including PSP, CBD and GGT. It is associated with 4R tau deposits in subpial or perivascular thorn-shaped astrocytes or granular fuzzy astrocytes in gray matter [130].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
In the citing paper
“The frequency of PART increases in the 80s and 90s when AD prevalence is level or declining [130].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [130]
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
Self-citationBlessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117
Weıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,894 · cited 6×
“A basic assumption is that AD is defined by 2 pathologic hallmarks: Ab amyloid plaques and tau neurofibrillary tangles (NFTs) (2).”
BackgroundMethodInfluentialSelf-citationArai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194
Observations on the brains of demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1970) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(70)90063-8 · Cited by 2,084
Flagged first, then by citations
1 of the 281 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- 10.1016/j.jalz.2014.10.008 · DOI · Paper page
- 10.1038/mp.2011.142mp2011142 · DOI
Cited by
Sorted by citations
Items 101–158 of 158
Towards a Biological Definition of Alzheimer Disease
Jellinger Kurt, A. (2019) · International Journal of Neurology and Neurotherapy · doi:10.23937/2378-3001/1410095 · Cited by 11
Rodrigo‐Herrero, S., Luque‐Tirado, A., Méndez-Barrio, C., García-Solís, D., Sánchez‐Arjona, M. B., Oropesa-Ruiz, J. M., Maillet, D., & Macías, E. F. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210115 · Cited by 9
Genetic associations with dementia‐related proteinopathy: Application of item response theory
Katsumata, Y., Fardo, D. W., Shade, L. M. P., Wu, X., Karanth, S. D., Hohman, T. J., Schneider, J. A., Bennett, D. A., Farfel, J. M., Gauthreaux, K. M., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13741 · Cited by 8
Self-citationTowards the virtual human patient. Quantitative Systems Pharmacology in Alzheimer's disease
Geerts, H., Spiros, Ä., Roberts, P., & Carr, R. A. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.05.062 · Cited by 9
Humphrey, W. O., Martindale, R., Pendlebury, W. W., & DeWitt, J. C. (2020) · Brain Pathology · doi:10.1111/bpa.12919 · Cited by 11
Rubí, S., Noguera, A., Tarongí, S., Oporto, M., García, A., Vico, H., Espino, A., Picado, M. J., Mas, A., Peña, C., et al. (2017) · Revista Española de Medicina Nuclear e Imagen Molecular · doi:10.1016/j.remn.2017.05.003 · Cited by 9
Limbic-predominant age-related TDP-43 encephalopathy (LATE)
Larner, A. J., & Griffiths, T. D. (2019) · Brain · doi:10.1093/brain/awz184 · Cited by 9
Kang, J., Luo, W., Zhang, C., Ren, Y., Cao, L., Wu, J. H., & Li, H. (2021) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2021.105790 · Cited by 8
Toniolo, S., Lorenzo, F. D., Bernardini, S., Mercuri, N. B., & Sancesario, G. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512151 · Cited by 8
Iacono, D., Geraci-Erck, M., Peng, H., & Bouffard, J. (2016) · Journal of Visualized Experiments · doi:10.3791/54602 · Cited by 8
Jamison, D., Kadamangudi, S., Tumurbaatar, B., Zhang, W.-R., Palmer, L. K., Kunkel, S., Kayed, R., Limón, A., & Taglialatela, G. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251352382 · Cited by 5
Rubí, S., Noguera, A., Tarongí, S., Oporto, M., García, A., Vico, H., Espino, A., Picado, M. J., Mas, A., Peña, C., et al. (2018) · Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) · doi:10.1016/j.remnie.2017.10.017 · Cited by 6
Kraner, S. D., Sompol, P. M., Prateeptrang, S., Promkan, M., Hongthong, S., Thongsopha, N., Nelson, P. T., & Norris, C. M. (2023) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2023.110012 · Cited by 5
Self-citationYang, Z. X., Sheng, J., Zhang, Q., Zhao, X., Song, Y., Dong, G., Zhang, R., Zhao, H., Wang, J., Pan, R., et al. (2025) · Journal of Integrative Neuroscience · doi:10.31083/jin26584 · Cited by 7
Primary age-related tauopathy in a Chinese cohort
Wang, X., Zhang, L., Lü, H., Wu, J., Liang, H., Liu, C., Tao, Q., Wu, Z., & Zhu, K. (2020) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900262 · Cited by 5
Dodich, A., Crespi, C., Santi, G. C., Marcone, A., Iannaccone, S., Perani, D., Cappa, S. F., & Cerami, C. (2021) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617721000254 · Cited by 5
Abulafia, C., Vidal, M. F., Olivar, N., Odzak, A. N., Brusco, I., Guinjoan, S. M., Cardinali, D. P., & Vigo, D. E. (2023) · Clinical Interventions in Aging · doi:10.2147/cia.s394749 · Cited by 6
Maioli, H., Mittenzwei, R., Shofer, J. B., Scherpelz, K. P., Marshall, D. A., Nolan, A., Nelson, P. T., Keene, C. D., & Latimer, C. S. (2023) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlad035 · Cited by 5
Self-citationNovel monoclonal antibodies targeting the RRM2 domain of human TDP-43 protein
Trejo‐Lopez, J. A., Sorrentino, Z. A., Riffe, C. J., Lloyd, G. M., Labuzan, S. A., Dickson, D. W., Yachnis, A. T., Prokop, S., & Giasson, B. I. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135353 · Cited by 5
Aging-Related Alterations in Language
Nadeau, S. E. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108554350.008 · Cited by 4
Seizures and Epilepsy in Dementia: Diagnosis and Management
Ritter, L. M., & Nilsson, C. (2021) · Springer eBooks · doi:10.1007/978-3-030-77904-7_12 · Cited by 4
Hanyu, H., Koyama, Y., Umekida, K., Momose, T., Watanabe, S., & Sato, T. (2024) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2024.122929 · Cited by 4
Jellinger, K. A. (2016) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000480 · Cited by 4
Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way
Pereira, P. E., Bleecker, J. D., Bogaert, E., & Dermaut, B. (2025) · Brain · doi:10.1093/brain/awaf076 · Cited by 3
Circular RNAs from the MAPT and TARDBP genes: Novel players in neurodegeneration?
Bagheri, N., Margvelani, G., Chiang, T.-W., Nelson, P. T., Chuang, T., & Stamm, S. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.106019 · Cited by 3
Self-citationBiomarkers, Cognitive Function, and Mortality in Centenarians
Shikimoto, R., Sasaki, T., Abe, Y., Tai, K., Hirose, N., Okano, H., & Arai, Y. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.11335 · Cited by 3
LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy
Ramanan, V. K., & Graff‐Radford, J. (2024) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001499 · Cited by 4
Tarai, S., Bit, A., Reis, H. J., Palotás, A., Rizvanov, A. A., & Bissoyi, A. (2016) · BioNanoScience · doi:10.1007/s12668-016-0240-y · Cited by 3
Mixed Pathologies in a Subject with a Novel PSEN1 G206R Mutation
Libard, S., Giedraitis, V., Kilander, L., Ingelsson, M., & Alafuzoff, I. I. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220655 · Cited by 3
Reframing TDP‐43 in Alzheimer's disease: From co‐pathology to neurovascular culprit
Donna, M. G. D., Motta, C., Bonomi, C. G., Bernocchi, F., Ricci, F., Poli, M., Koch, G., & Martorana, A. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70988 · Cited by 2
Pathology vs pathogenesis: Rationale and pitfalls in the clinicopathology model of neurodegeneration
Donadio, V. A., Sturchio, A., Rizzo, G., Abu‐Rumeileh, S., Liguori, R., & Espay, A. J. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-323-85538-9.00001-8 · Cited by 2
Garliyev, V., Lyssenko, C. A., Wiener, J. P., Praticò, D., & Lyssenko, N. N. (2024) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlae060 · Cited by 2
Association of late‐life variability in hemoglobin A1C with postmortem neuropathologies
Biswas, R., Capuano, A. W., Mehta, R. I., Bennett, D. A., & Arvanitakis, Z. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14471 · Cited by 2
Alzheimer's disease risk: amyloid versus neurodegeneration
Bischof, G. N. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30138-7 · Cited by 2
Anatomic and Histological Changes of the Aging Brain
Yachnis, A. T. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108554350.002 · Cited by 1
Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world
Iwase, T., Yoshida, M., Hashizume, Y., Inagaki, T., & Iwasaki, Y. (2022) · Neuropathology · doi:10.1111/neup.12874 · Cited by 1
Thompson, J., & Johnson, P. K. (2026) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlag079 · Cited by 1
Neuropathological Insights Into the Link Between Type 2 Diabetes and Dementia
Pruzin, J. J., Nelson, P. T., Abner, E. L., & Arvanitakis, Z. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809454-9.00006-8 · Cited by 1
Self-citationBrain pathological changes from population-based studies
Cao, Y., Huang, M., Shu, M.-J., & Zhu, Y. (2022) · Human Brain · doi:10.37819/hb.001.001.0205 · Cited by 1
Gan, E. H., & Razvi, S. (2017) · Gland Surgery · doi:10.21037/gs.2017.05.01 · Cited by 1
Limbic-predominant age-related TDP-43 encephalopathy (LATE)
Deng, F. M., Gaillard, F., & Sharma, R. (2019) · Radiopaedia.org · doi:10.53347/rid-70377 · Cited by 1
Dodich, A., Crespi, C., Santi, G. C., Marcone, A., Iannaccone, S., Perani, D., Cappa, S. F., & Cerami, C. (2020) · doi:10.31234/osf.io/u9ze3 · Cited by 1
Studying Vascular Morphologies in the Aged Human Brain Using Large Autopsy Datasets
Ighodaro, E. T. (2018) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2018.049
Self-citationIwasaki, Y., Deguchi, A., Mori, K., Ito, M., Kawai, Y., Akagi, A., Mimuro, M., Miyahara, H., & Yoshida, M. (2018) · Neuropathology · doi:10.1111/neup.12521
Brain pathology of centenarians and supercentenarians
Takao, M. (2018) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.55.562
Neuropathology of Alzheimer’s Disease and Vascular Dementia
Kapasi, A., & Schneider, J. A. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190634230.003.0015
MiRNA:RBP Interplay as a Key Regulatory Element in Health and Disease
Teneche, M. G., Carbó, N., & Casado, F. J. (2020) · COSMOS · doi:10.1142/s2591722620400098
Ashford, J. W. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734280398.793553881
Bednorz, A., & Derejczyk, J. (2023) · Neuropsychiatria i Neuropsychologia · doi:10.5114/nan.2023.129074
Brain Banking in Dementia Studies
Işık, A. T., Kaya, D., & Gökden, M. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3774-6_17
TDP-43 in aging and Alzheimer’s disease
Castellani, R. J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-99651-8.00012-0
Iso‐Markku, P., Drouard, G., Farrahi, V., Varjonen, A., Vähä‐Ypyä, H., Vasankari, T. J., Kaprio, J. A., Vuoksimaa, E., & Aaltonen, S. (2026) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbag065 · Cited by 1
Rubinski, A., Franzmeier, N., Neitzel, J., & Ewers, M. (2020) · Figshare · doi:10.6084/m9.figshare.13115315
CSF TDP-43: A Novel Biomarker for Limbic-Predominant Age-Related TDP-43 EncephalopathyPreprint
Fischer, A., Flosbach, F., Root, E., Breitbarth, M., Göricke, B., Schmitz, M., Hermann, P., & Zerr, I. (2026) · medRxiv · doi:10.64898/2026.05.07.26352671
Wu, L., Akingbade, T. O., Nelson, P. T., Wang, S. J., & Xu, B. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03027-0
Self-citationAgeing-related tau astrogliopathy in a population-based study of the oldest old (Vantaa 85+)
Englert, B., Savola, S. E., Tuimala, J., Colangelo, K., Mikhailenko, E., Puttonen, H., Tynninen, O., & Myllykangas, L. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107538
Erinacine C Attenuates Alzheimer’s-like Pathology: A Study in APP/PS1 Mice and PC12 Cells
Wang, L.-Y., Yeh, S.-L., Hsu, S.-T., Huang, S., Chau, C., & Chuang, C. (2026) · Molecules · doi:10.3390/molecules31183154
Neuropathology of centenarians and supercentenarians: An autopsy study
Magaki, S., Tung, S., Sinclair, D. J., Williams, C. K., Paganini‐Hill, A., Murillo, A., Aung, S., Goldstein, J., Vulcain, D. R., Salamon, N., et al. (2026) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2026.09.005
Metadata
- Authors
- Nelson, P. T., Trojanowski, J. Q., Abner, E. L., Al-Janabi, O. M., Jicha, G. A., Schmitt, F. A., Smith, C. D., Fardo, D. W., Wang, W.-X., Kryscio, R. J., Neltner, J. H., Kukull, W. A., Cykowski, M. D., Van Eldik, L. J., & Ighodaro, E. T.
- Affiliations
- Houston Methodist (US)
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-05-21
- Volume
- 75
- Issue
- 6
- Pages
- 482-498
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC6366658
- OpenAlex
- W2400971574
- Cited by
- 158
- References
- 281
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 6 · 2023: 12 · 2022: 11 · 2021: 11 · 2020: 21 · 2019: 19 · 2018: 28 · 2017: 21 · 2016: 10
- FWCI
- 23.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute on Aging (P30AG028383, U01AG016976, P30AG010124, P01AG017586, K25AG043546, U19AG010483)
- National Institute of Neurological Disorders and Stroke (F30NS090714)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, primary age-related tauopathy, TDP-43 pathology, CART, disease classification, genetic risk factors, gene regulatory networks, TMEM106B, ABCC9, arteriolosclerosis, oldest old, cognitive impairment
- MeSH terms
- Aged, 80 and over, Aging, Alzheimer Disease, Animals, DNA-Binding Proteins, Female, Hippocampus, Humans, Sclerosis, Tauopathies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
