Implications of Thal Amyloid Phase Across Alzheimer’s Disease
Alzheimer’s disease is a multi-proteinopathy, involving both extracellular amyloid-β deposits (i.e. amyloid-β plaques) and intracellular accumulation of post-translationally modified tau proteins. Both proteins are considered to develop in a topographic pattern that can be stereotypically assessed using Thal amyloid phase for amyloid-β plaques and Braak NFT staging.
A recent study in the Brain journal, conducted by researchers in Mayo Clinic Jacksonville, first author Melissa Murray, Ph.D., evaluates the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort and examines the relevance of Thal amyloid phase in a prospectively followed autopsied cohort who underwent ante-mortem.
The Mayo Clinic Jacksonville Brain Bank case series was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. 11C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within two years of death, while cortical 11C-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, cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. In these Alzheimer's disease cases, 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 11C-Pittsburgh compound B standard uptake value ratio.
In the 35 cases with ante-mortem amyloid imaging, a transition between Thal amyloid phases one to two seemed to correspond to 11C-Pittsburgh compound B standard uptake value ratio of 1.4. 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 11C-Pittsburgh compound B values, but not Braak tangle stage or cerebral amyloid angiopathy. The 11C-Pittsburgh compound B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of one to two.
Additional Mayo Clinic authors include: Val Lowe, M.D., Neill Graff-Radford, M.D., Amanda Liesinger, Ashley Cannon, Ph.D., Scott Przybelski, Bhupendra Rawal, Joseph Parisi, M.D., Ronald Petersen, M.D., Ph.D., Kejal Kantarci, M.D., Owen Ross, Ph.D., David Knopman, M.D., Clifford Jack, M.D., and Dennis Dickson, M.D.