Acta Neuropathologica

, Volume 126, Issue 3, pp 365–384 | Cite as

Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series

  • Gabor G. Kovacs
  • Ivan Milenkovic
  • Adelheid Wöhrer
  • Romana Höftberger
  • Ellen Gelpi
  • Christine Haberler
  • Selma Hönigschnabl
  • Angelika Reiner-Concin
  • Harald Heinzl
  • Susanne Jungwirth
  • Wolfgang Krampla
  • Peter Fischer
  • Herbert Budka
Original Paper

Abstract

Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-β (Aβ), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77–87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aβ deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aβ parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.

Keywords

Alzheimer’s disease Amyloid-β α-Synuclein Tau TDP-43 Community-based Protein-coding 

Supplementary material

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Supplementary material 2 (PDF 91 kb)
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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Gabor G. Kovacs
    • 1
  • Ivan Milenkovic
    • 1
  • Adelheid Wöhrer
    • 1
  • Romana Höftberger
    • 1
  • Ellen Gelpi
    • 1
    • 7
  • Christine Haberler
    • 1
  • Selma Hönigschnabl
    • 2
  • Angelika Reiner-Concin
    • 2
  • Harald Heinzl
    • 3
  • Susanne Jungwirth
    • 4
  • Wolfgang Krampla
    • 5
  • Peter Fischer
    • 6
  • Herbert Budka
    • 1
    • 8
  1. 1.Institute of NeurologyMedical University ViennaViennaAustria
  2. 2.Institute of PathologyDanube HospitalViennaAustria
  3. 3.Center for Medical Statistics, Informatics, and Intelligent SystemsMedical University ViennaViennaAustria
  4. 4.Ludwig Boltzmann Institute of Ageing ResearchViennaAustria
  5. 5.Department of RadiologyDanube HospitalViennaAustria
  6. 6.Psychiatric DepartmentMedical Research Society Vienna, D.C., Danube HospitalViennaAustria
  7. 7.Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  8. 8.Institute of NeuropathologyUniversity Hospital ZurichZurichSwitzerland

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