Comparative survey of the topographical distribution of signature molecular lesions in major neurodegenerative diseases

Steven E. Arnold, Jon B. Toledo, Dina H. Appleby, Sharon X. Xie, Li San Wang, Young Baek, David A. Wolk, Edward B. Lee, Bruce L. Miller, Virginia M.Y. Lee, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


An understanding of the anatomic distributions of major neurodegenerative disease lesions is important to appreciate the differential clinical profiles of these disorders and to serve as neuropathological standards for emerging molecular neuroimaging methods. To address these issues, here we present a comparative survey of the topographical distribution of the defining molecular neuropathological lesions among 10 neurodegenerative diseases from a large and uniformly assessed brain collection. Ratings of pathological severity in 16 brain regions from 671 cases with diverse neurodegenerative diseases are summarized and analyzed. These include: 1) amyloid-β and tau lesions in Alzheimer's disease; 2) tau lesions in three other tauopathies including Pick's disease, progressive supranuclear palsy and corticobasal degeneration; 3) α-synuclein inclusion ratings in four synucleinopathies including Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies, and multiple system atrophy; and 4) TDP-43 lesions in two TDP-43 proteinopathies, including frontotemporal lobar degeneration associated with TDP-43 and amyotrophic lateral sclerosis. The data presented graphically and topographically confirm and extend previous pathological anatomic descriptions and statistical comparisons highlight the lesion distributions that either overlap or distinguish the diseases in each molecular disease category.

Original languageEnglish (US)
Pages (from-to)4339-4355
Number of pages17
JournalJournal of Comparative Neurology
Issue number18
StatePublished - Dec 15 2013


  • Alzheimer's disease
  • Amyloid-β
  • Amyotrophic lateral sclerosis
  • Corticobasal degeneration
  • Dementia with Lewy bodies
  • Frontotemporal lobar degeneration
  • Multiple system atrophy
  • Parkinson's disease
  • Parkinson's disease with dementia
  • Pick's disease
  • Progressive supranuclear palsy
  • Tau α-synuclein
  • TDP
  • TDP-43

ASJC Scopus subject areas

  • Neuroscience(all)


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