beta-Amyloid discordance of cerebrospinal fluid and positron emission tomography imaging shows distinct spatial tau patterns

Extracellular beta-amyloid plaques and intracellular neurofibrillary tau tangles are the primary hallmarks of Alzheimer's disease. beta-Amyloid pathology can be directly quantified by positron emission tomography imaging or indirectly by measuring the decrease of cerebrospinal fluid beta-amyloid(42)/beta-amyloid(40) ratio. Although these two beta-amyloid biomarkers may be considered interchangeable, they sometimes show discordance, particularly in early stage of Alzheimer's disease. Individuals with cerebrospinal fluid beta-amyloid positive only or beta-amyloid positron emission tomography positive only may be at early amyloidosis stage compared to those who are cerebrospinal fluid beta-amyloid negative and beta-amyloid positron emission tomography negative orcerebrospinal fluid beta-amyloid positive and beta-amyloid positron emission tomography positive. Besides, beta-amyloid pathology may play an initiating role in Alzheimer's disease onset, leading to subsequent tau increases. However, it is still unclear whether individuals with different beta-amyloid pathways have distinct spatial patterns of cortical tau tangles in early amyloidosis stage. In this study, we analyzed 238 cognitively unimpaired and 77 mild cognitive impairment individuals with concurrent (interval of acquisition <1 year) F-18-flortaucipir tau positron emission tomography, beta-amyloid (F-18-florbetapir or F-18-florbetaben) positron emission tomography and cerebrospinal fluid beta-amyloid(42) and beta-amyloid(40) and cerebrospinal fluid p-Tau(181) and divided them into four different cerebrospinal fluid/positron emission tomography groups based on the abnormal status of cerebrospinal fluid beta-amyloid(42)/beta-amyloid(40) (cerebrospinal fluid +/-) and beta-amyloid positron emission tomography (+/-). We determined the cortical regions with significant tau elevations of different cerebrospinal fluid/positron emission tomography groups and investigated the region-wise and voxel-wise associations of tau positron emission tomography images with cerebrospinal fluid beta-amyloid(42)/beta-amyloid(40), beta-amyloid positron emission tomography and cerebrospinal fluid p-Tau/beta-amyloid(40) in early (cerebrospinal fluid positive/positron emission tomography negative and cerebrospinal fluid negative/positron emission tomography positive) and late (cerebrospinal fluid positive/positron emission tomography positive) amyloidosis stages. By compared to the cerebrospinal fluid negative/positron emission tomography negative individuals (Ref) without evidence of tau increase measured by cerebrospinal fluid or positron emission tomography, cerebrospinal fluid positive/positron emission tomography negative individuals showed higher tau in entorhinal but not in Braak(III/IV) and Braak(V/VI), whereas cerebrospinal fluid negative/positron emission tomography positive individuals had significant tau elevations in Braak(V/VI) but not in entorhinal and Braak(III/IV). In contrast, cerebrospinal fluid positive/positron emission tomography positive individuals showed significant tau increases in all the cortical regions than the Ref group. The voxel-wise analyses provided further evidence that lower cerebrospinal fluid beta-amyloid(42)/beta-amyloid(40) was associated with higher tau in entorhinal, whilst higher beta-amyloid positron emission tomography was related to higher tau in Braak(V/VI) regions in early amyloidosis stage. Both lower cerebrospinal fluid beta-amyloid(42)/beta-amyloid(40) and higher beta-amyloid positron emission tomography were correlated with tau aggregation in all the Braak stages regions in late amyloidosis stage. These findings provide novel insights into the spatial patterns of cortical tau tangles in different amyloidosis stages of Alzheimer's disease, suggesting cerebrospinal fluid beta-amyloid and beta-amyloid positron emission tomography discordant groups may have distinct characteristics of cortical tau tangles in early amyloidosis stage.