Neuropathology of autosomal dominant Alzheimer disease in the national Alzheimer coordinating center database

John M. Ringman*, Sarah Monsell, Denise W. Ng, Yan Zhou, Andy Nguyen, Giovanni Coppola, Victoria Van Berlo, Mario F. Mendez, Spencer Tung, Sandra Weintraub, Marek Marsel Mesulam, Eileen H. Bigio, Darren R. Gitelman, Amanda O. Fisher-Hubbard, Roger L. Albin, Harry V. Vinters

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p=0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal b-amyloid protein precursor processing.

Original languageEnglish (US)
Pages (from-to)284-290
Number of pages7
JournalJournal of neuropathology and experimental neurology
Issue number3
StatePublished - Mar 2016


  • Alzheimer disease
  • Amyloid plaques
  • Autosomal dominant
  • Cerebral amyloid angiopathy
  • Neurofibrillary tangles
  • Neuropathology
  • P267A

ASJC Scopus subject areas

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


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