Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [¹¹C]PBB3‐PET study

Abstract

IntroductionAmyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear.MethodsAssociations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [11C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [11C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(−)-cognitive healthy controls (HCs).ResultsHigh tau burden was associated with aging and low-level education in PiB(−)-HC and AD-spectrum groups, and with high Aβ burden and low-level education in all subjects. It was not Aβ but tau accumulation that showed significant associations with cognitive performance even in PiB(−)-HC.DiscussionThe present study indicated aging and low-level education after Aβ would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain

“…However, early in vitro evidence to date excludes this possibility [9], although more detailed in vitro competition studies are lacking for further validating the tracer specificity. Additionally, an earlier study that focused on a generally older, more severely affected sample of patients did not show a relationship between 11 C-PBB3 binding and amyloid-beta burden globally, indicating that the latter relationship could occur only in the early stages of the disease or in distinct brain regions [10]. Indeed, in our study, the regional correlations between 11 C-PBB3 and 11 C-AZD2184 binding were limited to the temporal and occipital lobes.…”

“…More specifically, both tau tracers were similarly correlated with MMSE score, as found in previous studies [10, 13, 44], although this did not apply to a more sensitive measure of global cognition: 11 C-THK5351 was more sensitive to declines in FSIQ than 11 C-PBB3. This is consistent with evidence suggesting that 11 C-THK5351 binding detects tau deposits that are more closely related to atrophy, consistent with post-mortem observations linking tau pathology to neurodegeneration [45, 46].…”

“…More specifically, this study was not designed to refute evidence found in earlier studies, which used larger sample sizes and therefore had greater power to investigate the exact strength of the relationships between the binding of the tracers and the different markers of the disease. In those studies, moderate correlations were found between (a) binding of tracers of the THK family and local amyloid-beta deposition in selected regions, (b) binding of 11 C-PBB3 and whole-brain grey matter atrophy, and (c) binding of both families of tracers with measures of episodic memory [10, 11, 13, 44]. Lastly, an important limitation of this study lies in the characteristics of the study sample – all participants were relatively young, apolipoprotein E ε4 carriers and had a clear AD-consistent CSF profile – which could limit substantially the generalizability of our findings in the diverse population of patients undergoing cognitive assessment in the clinical setting.…”

“…The results have indicated that the regional patterns of tau tracer binding are different from those of amyloid-beta tracers, although regional correlations exist [8–11]. Furthermore, the binding of all tau tracers is related to cognitive decline as well as regional neurodegeneration [8, 10–13]; this association becomes more obvious as neurodegeneration advances, as shown by the only longitudinal study [14]. However, since all these investigations were performed in individual cohorts using different tau tracers, it remains unclear whether the relationship between the tracers and the other markers of AD would be different when examined in a head-to-head design.…”

[IC‐P‐183]: NETWORKS OF TAU DISTRIBUTION IN ALZHEIMER's DISEASE

“…This finding points towards a specific deleterious effect as soon as tau pathology strikes visual cortical brain regions Braak, 1991, 1995) underscoring the regional specificity of a tau-cognition relationship. Moreover, these findings are consistent with recent findings reporting a relationship between cognitive function and regional tau pathology (Brier et al, 2016;Ossenkoppele et al, 2016;Shimada et al, 2017). To achieve a more fine-grained characterization of distinct cognitive profiles in Alzheimer's disease, future studies may employ an elaborate neuropsychological assessment and examine its correspondence with the TPNs identified here.…”