A Novel ITM2B Mutation Associated with Familial Chinese Dementia

2021 ◽  
pp. 1-7
Author(s):  
Xin Liu ◽  
Ke-Liang Chen ◽  
Yi Wang ◽  
Yu-Yuan Huang ◽  
Shi-Dong Chen ◽  
...  
Keyword(s):  
Tau Protein ◽  
Clinical Phenotype ◽  
Amyloid Pet ◽  
Genetic Knowledge ◽  
Familial British Dementia ◽  
Familial Danish Dementia ◽  
Tau Pet ◽  
Ethnic Distribution ◽  
Familial Dementia

Mutations in ITM2B have been found to be associated with familial Danish dementia (FDD) and familial British dementia (FBD). Here, we describe a patient with dementia caused by a novel ITM2B p. *267Leuext *11 mutation. The patient presented with dementia, ataxia, deafness, and paraplegia. Amyloid PET and Tau PET showed abnormal deposition of amyloid and tau protein in brain. Summarized from previous 26 FBD and FDD cases, the clinical phenotype of ITM2B; p. *267Leuext *11 mutation in ITM2B is different from the features of FBD and FDD. Our findings increased genetic knowledge of familial dementia and extend the ethnic distribution of ITM2B mutations.

scholarly journals Longitudinally Increasing Elevated Asymmetric Flortaucipir Binding in a Cognitively Unimpaired Amyloid-Negative Older Individual

2021 ◽  
pp. 1-6
Author(s):  
Christopher G. Schwarz ◽  
David S. Knopman ◽  
Vijay K. Ramanan ◽  
Val J. Lowe ◽  
Heather J. Wiste ◽  
...  
Keyword(s):  
Risk Factors ◽  
Amyloid Pet ◽  
Imaging Findings ◽  
Tau Pet

We present the case of a cognitively unimpaired 77-year-old man with elevated, asymmetric, and longitudinally increasing Flortaucipir tau PET despite normal (visually negative) amyloid PET. His atypical tau PET signal persisted and globally increased in a follow-up scan five years later. Across eight years of observations, temporoparietal atrophy was observed consistent with tau PET patterns, but he retained the cognitively unimpaired classification. Altogether, his atypical tau PET signal is not explained by any known risk factors or alternative pathologies, and other imaging findings were not remarkable. He remains enrolled for further observation.

scholarly journals Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

2021 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

scholarly journals Topographic Distribution of Amyloid-β, Tau, and Atrophy in Patients With Behavioral/Dysexecutive Alzheimer Disease

Neurology ◽  
2020 ◽  
Vol 96 (1) ◽  
pp. e81-e92
Author(s):  
Joseph Therriault ◽  
Tharick A. Pascoal ◽  
Melissa Savard ◽  
Andrea L. Benedet ◽  
Mira Chamoun ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Clinical Symptoms ◽  
Characteristic Curve ◽  
Tertiary Care ◽  
Amyloid Β ◽  
Executive Dysfunction ◽  
Anterior Cingulate ◽  
Amyloid Pet ◽  
Clinical Criteria ◽  
Tau Pet

ObjectiveTo determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms.MethodsWe assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity– and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing.ResultsVoxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction.ConclusionsOur results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.

scholarly journals Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Neurology ◽  
2019 ◽  
Vol 93 (1) ◽  
pp. e29-e39 ◽  
Author(s):  
Val J. Lowe ◽  
Tyler J. Bruinsma ◽  
Heather J. Wiste ◽  
Hoon-Ki Min ◽  
Stephen D. Weigand ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Memory Performance ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Population Based ◽  
Cognitive Test ◽  
Amyloid Pet ◽  
Cross Sectional ◽  
Tau Pet

ObjectiveTo assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.MethodsTau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.ResultsHigher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.ConclusionsTau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

scholarly journals Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz2387 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Emelie Andersson ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Philip Insel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
Tau Pet ◽  
5Xfad Mice ◽  
Tau Aggregation ◽  
T Tau

The links between β-amyloid (Aβ) and tau in Alzheimer’s disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

scholarly journals Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

2020 ◽  
Vol 12 (524) ◽  
pp. eaau5732 ◽  
Author(s):  
Renaud La Joie ◽  
Adrienne V. Visani ◽  
Suzanne L. Baker ◽  
Jesse A. Brown ◽  
Viktoriya Bourakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Specific Distribution ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
Β Amyloid ◽  
Tau Pet ◽  
Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

scholarly journals A Study on PHF-Tau Network Effected by Apolipoprotein E4

2020 ◽  
Vol 35 ◽  
pp. 153331752097141
Author(s):  
Yuan Li ◽  
Zhijun Yao ◽  
Yongqing Yang ◽  
Feng Zhao ◽  
Yu Fu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Tau Protein ◽  
Paired Helical Filaments ◽  
Brain Regions ◽  
Primary Role ◽  
Node Failure ◽  
Random Node ◽  
Network Properties ◽  
Tau Pet

Apolipoprotein E 4 Allele (APOE 4) is an important factors in Mild cognitive impairment (MCI) and Alzheimer’s disease(AD). It plays a primary role in abnormal modification of aggregated Tau protein-paired helical filaments Tau (PHF-Tau). In this study, 143 subjects with PHF-Tau PET were divided into 2 groups (APOE 4 carriers and noncarriers). The measurements of the PHF-Tau network properties and resilient were calculated for 2 group networks respectively. APOE 4 carriers group showed significant differences in all the network properties in the results. We also found significant differences of betweenness centrality in some brain regions for APOE 4 carriers. Moreover, the APOE 4 carriers showed less resilient to targeted or random node failure. Our results indicated that the effects of APOE 4 may lead to abnormalities of PHF-Tau protein network. These findings may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.

scholarly journals Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
L. Lemoine ◽  
A. Ledreux ◽  
E. J. Mufson ◽  
S. E. Perez ◽  
G. Simic ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Binding Properties ◽  
Pet Tracers ◽  
Binding Characteristics ◽  
Age Related ◽  
Autopsy Brain Tissue ◽  
Tau Pet

Abstract Introduction Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD. Methods Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo. Results The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites. Conclusions This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.

IC-P-156: Baseline amyloid PET imaging, longitudinal amyloid accumulation, and Tau PET imaging in preclinical Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_2) ◽  
pp. P105-P105
Author(s):  
Aaron P. Schultz ◽  
Elizabeth C. Mormino ◽  
Jasmeer P. Chhatwal ◽  
Molly LaPoint ◽  
Alex S. Dagley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Amyloid Pet ◽  
Preclinical Alzheimer’S Disease ◽  
Amyloid Accumulation ◽  
Tau Pet ◽  
Tau Pet Imaging ◽  
Amyloid Pet Imaging
Sign in / Sign up

Export Citation Format

Share Document