In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum.
To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image-based tau staging in the Alzheimer disease (AD) spectrum.



We included 195 participants (53 AD, 52 amnestic mild cognitive impairment [MCI], 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans ((18) F-florbetaben for amyloid-β and (18) F-AV-1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image-based tau stage based on the Z score of the composite region for each stage.



Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image-based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI.



Our PET study replicated postmortem spreading patterns of tau and amyloid-β pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image-based tau staging may be useful for the objective assessment of AD progression. Ann Neurol 2016;80:247-258.
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
Hanna
H
Cho
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine.
Jae Yong
JY
Choi
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
Mi Song
MS
Hwang
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
You Jin
YJ
Kim
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
Hye Mi
HM
Lee
Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
Hye Sun
HS
Lee
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine.
Jae Hoon
JH
Lee
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine.
Young Hoon
YH
Ryu
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
Myung Sik
MS
Lee
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine.
Chul Hyoung
CH
Lyoo
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000647:Amnesia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000378:metabolism*
D000682:Amyloid; D016875:tau Proteins