Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease: The Hisayama study

Hamasaki, Hideomi; Honda, Hiroki; Suzuki, Satoshi; Shijo, Masahiro; Ohara, Tomoyuki; Hatabe, Yozo; Okamoto, Tsukasa; Ninomiya, Toshiharu; Iwaki, Toru

doi:10.1016/j.dadm.2019.04.008

Cited by 15 publications

(12 citation statements)

References 34 publications

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“… 53 Although we cannot rule out non-specific binding or off-target binding, the clear basal ganglia [ 18 F]PI-2620 binding pattern of some AD cases (∼30%) could be explained by a recent Japanese autopsy study, which reported on the presence of tau in the basal ganglia of AD cases. 54 Our current data support the hypothesis that even low deposition of 3/4R tau in the basal ganglia of AD could cause a higher PET signal when compared to strong 4R tau deposition in the basal ganglia of PSP cases.…”

Section: Discussionsupporting

confidence: 88%

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Song

Beyer

Kaiser

et al. 2021

J Cereb Blood Flow Metab

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The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [18F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.

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Section: Discussionsupporting

confidence: 88%

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Song

Beyer

Kaiser

et al. 2021

J Cereb Blood Flow Metab

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“…This was driven by 3 subjects with increased uptake in the basal ganglia and also significant neocortical tracer uptake (subjects 13, 17, and 20). Two recent autopsy studies have shown tau deposition in the basal ganglia of subjects with advanced AD (Braak V/VI) (33,34). As such, uptake in subcortical regions in advanced AD is not unexpected and should not occur in the absence of significant neocortical uptake.…”

Section: Discussionmentioning

confidence: 96%

Tau PET imaging with ¹⁸F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study

Mueller¹,

Bullich²,

et al. 2019

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18 F-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative disorders. Preclinically, 18 F-PI-2620 binds to both 3-repeat and 4-repeat tau isoforms. The purpose of this firstin-humans study was to evaluate the ability of 18 F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess the safety and tolerability of this new tau PET tracer. Methods: Participants with a clinical diagnosis of probable AD and healthy controls (HCs) underwent dynamic 18 F-PI-2620 PET imaging for 180 min. 18 F-PI-2620 binding was assessed visually and quantitatively using distribution volume ratios (DVR) estimated from noninvasive tracer kinetics and SUV ratio (SUVR) measured at different time points after injection, with the cerebellar cortex as the reference region. Time-activity curves and SUVR were assessed in AD and HC subjects, as well as DVR and SUVR correlations and effect size (Cohen's d) over time. Results: 18 F-PI-2620 showed peak brain uptake around 5 min after injection and fast washout from nontarget regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD subjects than in HCs. Very low background signal was observed in HCs. 18 F-PI-2620 administration was safe and well tolerated. SUVR time-activity curves in most regions and subjects achieved a secular equilibrium after 40 min after injection. A strong correlation (R 2. 0.93) was found between noninvasive DVR and SUVR for all imaging windows starting at more than 30 min after injection. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. 18 F-PI-2620 uptake in neocortical regions significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC subjects demonstrated a high image quality and excellent signal-to-noise ratio of 18 F-PI-2620 PET for imaging tau deposition in AD subjects. Noninvasive quantification using DVR and SUVR for 30-min imaging windows between 30 and 90 min after injection-for example, 45-75 min-provides robust and significant discrimination between AD and HC subjects. 18 F-PI-2620 uptake in expected regions correlates strongly with neurocognitive performance.

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“…Previous studies have demonstrated the deposition of amyloid β or tau pathology in the striatum in patients with advanced AD [15,16]. Attems et al [17] demonstrated that patients with AD had a high rate of α-synuclein pathology, which caused loss of dopamine neurons in the nigrostriatal pathway.…”

Section: Discussionmentioning

confidence: 99%

Apathy in Alzheimer’s Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei

Udo

Hashimoto

Toyonaga

et al. 2020

Dement Geriatr Cogn Disord Extra

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Introduction: Apathy is a common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The striatal binding potential (BP) of 123 I-FP-CIT (N-δ-fluoropropyl-2βcarbomethoxy-3β-[4-iodophenyl]tropane) single-photon emission computed tomography (SPECT) is correlated with the degree of apathy in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). This study aimed to determine if dopaminergic activity in the basal ganglia is associated with the development of apathy in AD. Methods: Nineteen subjects with AD were included and underwent 123 I-FP-CIT-SPECT. Patients with other types of dementia as a comorbidity, those taking antidepressants, and those with overt parkinsonism were excluded. Apathy was assessed using the Apathy Evaluation Scale Informant-Japanese version (AES-I-J). SPECT images were overlaid with images in striatal regions of interest (ROIs), and the SPECT values in these regions were counted. The relationship between BP values and AES-I-J scores was investigated using Spearman's rank correlation coefficient. Results: Significant inverse correlations were observed between BP values and AES-I-J scores in the left caudate nucleus and there was a marginally significant inverse correlation in the right caudate nucleus. Conclusion: The pathological basis of apathy might be the impairment of the dopaminergic nervous system. Further studies on more subjects with AD, healthy controls, and patients with PD and DLB are needed.

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Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease: The Hisayama study

Cited by 15 publications

References 34 publications

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Tau PET imaging with ¹⁸F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study

Apathy in Alzheimer’s Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei

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Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease: The Hisayama study

Cited by 15 publications

References 34 publications

Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study

Apathy in Alzheimer’s Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei

Contact Info

Product

Resources

About

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Binding characteristics of [¹⁸F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Tau PET imaging with ¹⁸F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study