Acta Neuropathologica Communications (Nov 2019)

Different aspects of Alzheimer’s disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia

  • Dietmar Rudolf Thal,
  • Alicja Ronisz,
  • Thomas Tousseyn,
  • Ajeet Rijal Upadhaya,
  • Karthikeyan Balakrishnan,
  • Rik Vandenberghe,
  • Mathieu Vandenbulcke,
  • Christine A. F. von Arnim,
  • Markus Otto,
  • Thomas G. Beach,
  • Johan Lilja,
  • Kerstin Heurling,
  • Aruna Chakrabarty,
  • Azzam Ismail,
  • Christopher Buckley,
  • Adrian P. L. Smith,
  • Sathish Kumar,
  • Gill Farrar,
  • Jochen Walter

DOI
https://doi.org/10.1186/s40478-019-0837-9
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 16

Abstract

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Abstract Alzheimer’s disease (AD)-related amyloid β-peptide (Aβ) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and undergoes qualitative changes in its composition of modified Aβ species throughout the pathogenesis of AD. It is not clear which of these aspects of Aβ pathology contribute to AD progression and to what extent amyloid positron emission tomography (PET) reflects each of these aspects. To address these questions three cohorts of human autopsy cases (in total n = 271) were neuropathologically and biochemically examined for the topographical distribution of Aβ pathology (plaques and CAA), its quantity and its composition. These parameters were compared with neurofibrillary tangle (NFT) and neuritic plaque pathology, the degree of dementia and the results from [18F]flutemetamol amyloid PET imaging in cohort 3. All three aspects of Aβ pathology correlated with one another, the estimation of Aβ pathology by [18F]flutemetamol PET, AD-related NFT pathology, neuritic plaques, and with the degree of dementia. These results show that one aspect of Aβ pathology can be used to predict the other two, and correlates well with the development of dementia, advancing NFT and neuritic plaque pathology. Moreover, amyloid PET estimates all three aspects of Aβ pathology in-vivo. Accordingly, amyloid PET-based estimates for staging of amyloid pathology indicate the progression status of amyloid pathology in general and, in doing so, also of AD pathology. Only 7.75% of our cases deviated from this general association.

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