scholarly journals High-contrast in-vivo imaging of tau pathologies in Alzheimer’s and non-Alzheimer’s disease tauopathies

2020 ◽  
Author(s):  
Kenji Tagai ◽  
Maiko Ono ◽  
Manabu Kubota ◽  
Soichiro Kitamura ◽  
Keisuke Takahata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Corticobasal Degeneration ◽  
Emission Tomography ◽  
High Contrast ◽  
Positron Emission ◽  
Tau Isoforms

AbstractDepositions of fibrillary tau protein aggregates are implicated in diverse tauopathies, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). A panel of radiochemicals has enabled in-vivo positron emission tomography (PET) of AD tau pathologies composed of all six tau isoforms, while sensitive detection of FTLD tau inclusions, mostly consisting of tau isoforms with three or four repeat domains only, has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing tau deposits with all isoform composites. In-vitro assays demonstrated the reactivity of this compound with tau pathologies in AD, four-repeat tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and three-repeat tauopathies represented by Pick’s disease (PiD). We could also utilize PM-PBB3 for bimodal, multiscale optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of radiolabeled 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant PSP tau topologies. Notably, the in-vivo reactivity of 18F-PM-PBB3 with three- and four-repeat tau lesions was strongly supported by neuropathological examinations of autopsied and biopsied brains derived from PiD, PSP and CBD patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of the neuropathological basis, composed of PSP, CBD and PiD, underlying the diverse clinical phenotypes of FTLD. Taking these findings together, we propose the new tau probe as a powerful tool for etiological, diagnostic and therapeutic PET assessments of the tau pathogenesis in AD and FTLD spectra at nonclinical and clinical levels.One Sentence SummaryWe developed a positron emission tomography probe for tau fibrils in an animal model and patients with Alzheimer’s disease and non-Alzheimer’s disease tauopathies with high contrast, enabling translational assessments of the tau pathogenesis and diagnostic evaluations of disease-specific and stage-dependent tau topologies on an individual basis.

scholarly journals In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H positron emission tomography

2019 ◽  
Vol 47 (2) ◽  
pp. 390-402 ◽  
Author(s):  
Christine Bastin ◽  
Mohamed Ali Bahri ◽  
François Meyer ◽  
Marine Manard ◽  
Emma Delhaye ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
Emission Tomography ◽  
Synaptic Loss ◽  
Positron Emission

IC-P-024: A novel positron emission tomography contrast agent targeting cathepsin d shows preferential in vivo retention in an Alzheimer's disease mouse model

2015 ◽  
Vol 11 (7S_Part_1) ◽  
pp. P26-P27
Author(s):  
Jonatan A. Snir ◽  
Mojmir Suchy ◽  
Geron A. Bindseil ◽  
Blaine A. Chronik ◽  
Robert H.E. Hudson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Mouse Model ◽  
Contrast Agent ◽  
Cathepsin D ◽  
Emission Tomography ◽  
Positron Emission

O1-02-05: A novel positron emission tomography contrast agent targeting cathepsin d shows preferential in vivo retention in an Alzheimer's disease mouse model

2015 ◽  
Vol 11 (7S_Part_3) ◽  
pp. P128-P128
Author(s):  
Jonatan A. Snir ◽  
Mojmir Suchy ◽  
Geron A. Bindseil ◽  
Blaine A. Chronik ◽  
Robert H.E. Hudson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Mouse Model ◽  
Contrast Agent ◽  
Cathepsin D ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Combined Study of Cerebral Glucose Metabolism and [11C]Methionine Accumulation in Probable Alzheimer's Disease Using Positron Emission Tomography

1996 ◽  
Vol 16 (3) ◽  
pp. 399-408 ◽  
Author(s):  
E. Salmon ◽  
M. C. Gregoire ◽  
G. Delfiore ◽  
C. Lemaire ◽  
C. Degueldre ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Glucose Metabolism ◽  
Clinical Symptoms ◽  
Synaptic Activity ◽  
Emission Tomography ◽  
Tissue Loss ◽  
Positron Emission

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measured with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.

scholarly journals Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 405
Author(s):  
Eva Bagyinszky ◽  
Hyon Lee ◽  
Jung Min Pyun ◽  
Jeewon Suh ◽  
Min Ju Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Emission Tomography ◽  
Korean Patients ◽  
Positron Emission ◽  
Mri Scans ◽  
Early Onset Alzheimer’S Disease

We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.

scholarly journals Longitudinal study of primary progressive aphasia in a patient with pathologically diagnosed Alzheimer’s disease: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Masahiko Takaya ◽  
Kazunari Ishii ◽  
Kazumasa Saigoh ◽  
Osamu Shirakawa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Longitudinal Study ◽  
Corticobasal Degeneration ◽  
Primary Progressive Aphasia ◽  
Emission Tomography ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Positron Emission

Abstract Background Alzheimer’s disease is a neurodegenerative disease involving the deposition of pathologic amyloid-β and tau protein in the cerebral cortex. Alzheimer’s disease is commonly characterized by progressive impairment of recent memory. Primary progressive aphasia is also often observed in patients with Alzheimer’s disease. Moreover, language-associated symptoms, such as primary progressive aphasia, are diverse and varied in Alzheimer’s disease. However, nonfluent/agrammatic variant primary progressive aphasia is not generally considered a symptom of Alzheimer’s disease. To date, there has been no longitudinal study of primary progressive aphasia in Japanese-speaking patients or in patients speaking other languages with pathologically diagnosed Alzheimer’s disease. Here we present a longitudinal study of primary progressive aphasia in a Japanese patient pathologically diagnosed with Alzheimer’s disease. Case presentation A 75-year-old Japanese man, whose wife reported that his memory was impaired, also suffered from suspected aphasia. He was pathologically diagnosed with Alzheimer’s disease using 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Based on clinical observation and the results of the Japanese standard language test of aphasia, he was also diagnosed with nonfluent/agrammatic variant primary progressive aphasia. During the subsequent 2 years, his cognitive impairment, aphasia, and behavioral and psychological symptoms of dementia progressed. Furthermore, progression of pathologic amyloid-β and tau protein deposition was revealed through 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Although the results of [123I] iodoamphetamine single-photon emission computed tomography suggested corticobasal degeneration, this was not observed on the [123I] FP-CIT single-photon emission computed tomography (SPECT) (DaTscan). A previous study had reported that Alzheimer’s disease with a nonfluent/agrammatic variant primary progressive aphasia was accompanied by corticobasal degeneration; however, this was not true in our case. Conclusions This is possibly the first longitudinal study of nonfluent/agrammatic variant primary progressive aphasia in a Japanese-speaking patient with pathologically diagnosed Alzheimer’s disease, but without corticobasal degeneration.

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