Clinicopathologic and <sup>11</sup>C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum

Melissa E Murray, Val Lowe, Neill R Graff Radford, Amanda M. Liesinger, Ashley Cannon, Scott A. Przybelski, Bhupendra Rawal, Joseph E Parisi, Ronald Carl Petersen, Kejal M Kantarci, Owen A Ross, Ranjan Duara, David S Knopman, Clifford R Jr. Jack, Dennis W Dickson

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing-Alzheimer's Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia published by the National Institute of Ageing-Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem <sup>11</sup>C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of <sup>11</sup>C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. <sup>11</sup>C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical <sup>11</sup>C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer's disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted <sup>11</sup>C-Pittsburgh compound B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition between Thal amyloid phases 1 to 2 seemed to correspond to <sup>11</sup>C-Pittsburgh compound B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer's disease cases who were older and were APOE-ε4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer's disease patients, the pre-mortem clinical status was driven by Braak tangle stage. Thal amyloid phase correlated best with <sup>11</sup>C-Pittsburgh compound B values, but not Braak tangle stage or cerebral amyloid angiopathy. The <sup>11</sup>C-Pittsburgh compound B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1-2.

Original languageEnglish (US)
Pages (from-to)1370-1381
Number of pages12
JournalBrain
Volume138
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Amyloid
Alzheimer Disease
Cerebral Amyloid Angiopathy
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Pittsburgh
Alzheimer's Disease
Autopsy
Guidelines
Amyloid Plaques
Brain
Age of Onset
Positron-Emission Tomography
Cerebellum
Cerebrospinal Fluid
Microscopy
Biomarkers

Keywords

  • Alzheimer's disease
  • Braak tangle stage
  • neuropathology
  • Pittsburgh compound B
  • Thal amyloid phase

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Clinicopathologic and <sup>11</sup>C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum. / Murray, Melissa E; Lowe, Val; Graff Radford, Neill R; Liesinger, Amanda M.; Cannon, Ashley; Przybelski, Scott A.; Rawal, Bhupendra; Parisi, Joseph E; Petersen, Ronald Carl; Kantarci, Kejal M; Ross, Owen A; Duara, Ranjan; Knopman, David S; Jack, Clifford R Jr.; Dickson, Dennis W.

In: Brain, Vol. 138, No. 5, 01.05.2015, p. 1370-1381.

Research output: Contribution to journalArticle

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