Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development

Gil D. Rabinovici, Maria C. Carrillo, Mark Forman, Susan DeSanti, David S. Miller, Nicholas Kozauer, Ronald C. Petersen, Christopher Randolph, David S. Knopman, Eric E. Smith, Maria Isaac, Niklas Mattsson, Lisa J. Bain, James A. Hendrix, John R. Sims

Research output: Contribution to journalShort surveypeer-review

45 Scopus citations


Dementia is often characterized as being caused by one of several major diseases, such as Alzheimer's disease (AD), cerebrovascular disease, Lewy body disease, or a frontotemporal degeneration. Failure to acknowledge that more than one entity may be present precludes attempts to understand interactive relationships. The clinicopathological studies of dementia demonstrate that multiple pathologic processes often coexist. How overlapping pathologic findings affect the diagnosis and treatment of clinical AD and other dementia phenotypes was the topic taken up by the Alzheimer's Association's Research Roundtable in October 2014. This review will cover the neuropathologic basis of dementia, provide clinical perspectives on multiple pathologies, and discuss therapeutics and biomarkers targeting overlapping pathologies and how these issues impact clinical trials.High prevalence of multiple pathologic findings among individuals with clinical diagnosis of AD suggests that new treatment strategies may be needed to effectively treat AD and other dementing illnesses.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Issue number1
StatePublished - Jan 1 2017


  • Alzheimer's disease (AD)
  • Cerebrovascular disease
  • Frontotemporal degeneration
  • Lewy body disease
  • TDP-43
  • Tau
  • α-Synuclein
  • β-amyloid

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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