Assessment of amyloid β in pathologically confirmed frontotemporal dementia syndromes

Tan, Rachel; Kril, Jillian J.; Yang, Yue; Tom, Nicole; Hodges, John R.; Villemagne, Victor L.; Rowe, Christopher C.; Leyton, Cristian E.; Kwok, John B.; Ittner, Lars M.; Halliday, Glenda M.

doi:10.1016/j.dadm.2017.05.005

Cited by 45 publications

(44 citation statements)

References 37 publications

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“…The larger discrepancy in Alzheimer's versus semantic dementia might also reflect a higher prevalence of co-pathologies in Alzheimer's disease versus semantic dementia. Indeed, even though the literature on co-pathologies in semantic dementia is still scarce, autopsy studies revealed that pathologically-confirmed frontotemporal dementia cases with semantic dementia rarely present with co-pathologies such as extracellular amyloid-β (Tan et al, 2017) or Alzheimer's disease pathology (Davies et al, 2005;Mesulam et al, 2014). Recent evidence from animal models even suggests that TDP-43 pathology is associated with reduced amyloid-β burden, possibly due to enhanced amyloid-β clearance (Paolicelli et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

et al. 2018

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Multimodal neuroimaging analyses offer additional information beyond that provided by each neuroimaging modality. Thus, direct comparisons and correlations between neuroimaging modalities allow revealing disease-specific topographic relationships. Here, we compared the topographic discrepancies between atrophy and hypometabolism in two neurodegenerative diseases characterized by distinct pathological processes, namely Alzheimer's disease (AD) versus semantic dementia (SD), to unravel their specific influence on local and global brain structure-function relationships. We found that intermodality topographic discrepancies clearly distinguished the two patient groups: AD showed marked discrepancies between both alterations, with greater hypometabolism than atrophy in large posterior associative neocortical regions, while SD showed more topographic consistency between atrophy and hypometabolism across brain regions. These findings likely reflect the multiple pathologies versus the relatively unitary pathological process underlying AD versus SD respectively. Our results evidence that multimodal neuroimaging-derived indexes can provide clinically relevant information to discriminate the two diseases, and potentially reveal distinct neuropathological processes.

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Section: Discussionmentioning

confidence: 99%

Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

et al. 2018

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“…Similar results have been obtained previously with PIB in FTD patients and with various amyloid tracers, including florbetapir, in AD patients. We believe that the early florbetapir frames provide important complementary diagnostic information to Aβ deposition, shown by late florbetapir frames, which may be present not only in patients with AD, but also cognitively normal elderly and occasionally as secondary pathology in other neurodegenerative diseases, including FTD [4]. …”

Section: Discussionmentioning

confidence: 99%

“…This is particularly true for frontotemporal dementia (FTD), which does not typically present with fibrillar amyloid-beta (Aβ) pathology. However, in some FTD patients, fibrillar Aβ deposits may be present in addition to the pathological hallmarks of FTD and the proportion of cases with both pathologies increases with age [4], therefore an additional differential diagnostic marker is needed.…”

Section: Introductionmentioning

confidence: 99%

Dual-phase [18F]florbetapir in frontotemporal dementia

Asghar

Hinz

Herholz

et al. 2018

Eur J Nucl Med Mol Imaging

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PurposeThe PET tracer [18F]florbetapir is a specific fibrillar amyloid-beta (Aβ) biomarker. During the late scan phase (> 40 min), it provides pathological information about Aβ status. Early scan phase (0–10 min) can provide FDG-‘like’ information. The current investigation tested the feasibility of using florbetapir as a dual-phase biomarker in behavioural variant frontotemporal dementia (bvFTD).MethodsEight bvFTD patients underwent [18F]florbetapir and [18]FDG-PET scans. Additionally, ten healthy controls and ten AD patients underwent florbetapir-PET only. PET data were acquired dynamically for 60-min post-injection. The bvFTD PET data were used to define an optimal time window, representing blood flow-related pseudo-metabolism (‘pseudo-FDG’), of florbetapir data that maximally correlated with the corresponding real FDG SUVR (40–60 min) in a composite neocortical FTD region.ResultsA 2 to 5-min time window post-injection of the florbetapir-PET data provided the largest correlation (Pearson’s r = 0.79, p = 0.02) to the FDG data. The pseudo-FDG images demonstrated strong internal consistency with actual FDG data and were also visually consistent with the bvFTD patients’ hypometabolic profiles. The ability to identify bvFTD from blind visual rating of pseudo-FDG images was consistent with previous reports using FDG data (sensitivity = 75%, specificity = 85%).ConclusionsThis investigation demonstrates that early phase florbetapir uptake shows a reduction of frontal lobe perfusion in bvFTD, similar to metabolic findings with FDG. Thus, dynamic florbetapir scans can serve as a dual-phase biomarker in dementia patients to distinguish FTD from AD and cognitively normal elderly, removing the need for a separate FDG-PET scan in challenging dementia cases.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4238-2) contains supplementary material, which is available to authorized users.

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“…In such cases amyloid PET can identify fibrillary amyloid as an indicator of AD. Fibrillary amyloid can also coexist with other pathologies, which is frequently the case in patients with DLB and vascular dementia (which might be termed mixed dementia), but is also possible with FTD and may possibly contribute to more rapid progression [451, 452]. Thus, if anti-amyloid therapy did eventually show clinical benefit in AD patients, patients with non-AD dementia and positive amyloid PET might also benefit.…”

Section: Contribution and Role Of Positron Emission Tomography (Pet)mentioning

confidence: 99%

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

Hampel

Toschi

Babiloni

et al. 2018

JAD

131

113

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The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

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Assessment of amyloid β in pathologically confirmed frontotemporal dementia syndromes

Cited by 45 publications

References 37 publications

Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

Dual-phase [18F]florbetapir in frontotemporal dementia

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

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