"New old pathologies": Ad, part, and cerebral age-related TDP-43 with sclerosis (CARTS)

Peter T. Nelson, John Q. Trojanowski, Erin L. Abner, Omar M. Al-Janabi, Gregory A. Jicha, Frederick A. Schmitt, Charles D. Smith, David W. Fardo, Wang Xia Wang, Richard J. Kryscio, Janna H. Neltner, Walter A. Kukull, Matthew D. Cykowski, Linda J. Van Eldik, Eseosa T. Ighodaro

Research output: Contribution to journalReview articlepeer-review

88 Scopus citations


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 agerelated 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.

Original languageEnglish (US)
Pages (from-to)482-498
Number of pages17
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
StatePublished - Jun 1 2016


  • Arteriosclerosis
  • Cerebrovascular disease
  • Frontotemporal lobar degeneration
  • Genome-wide association study
  • Neurofibrillary tangles
  • Plaques
  • VCID

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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