scholarly journals Corrigendum to: CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease

Brain ◽  
2021 ◽  
Author(s):  
Kanta Horie ◽  
Nicolas R Barthélemy ◽  
Chihiro Sato ◽  
Randall J Bateman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Binding Region ◽  
Microtubule Binding ◽  
Clinical Stages

scholarly journals CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease

Brain ◽  
2020 ◽  
Author(s):  
Kanta Horie ◽  
Nicolas R Barthélemy ◽  
Chihiro Sato ◽  
Randall J Bateman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Extraction Methods ◽  
Upstream Region ◽  
Chemical Extraction ◽  
Binding Region ◽  
Microtubule Binding ◽  
Highly Correlated ◽  
Tau Aggregation

Abstract Tau is a microtubule associated protein in the brain that aggregates in Alzheimer’s disease to form pathological tangles and neurites. Insoluble tau aggregates composed of the microtubule binding region (MTBR) of tau are highly associated with the cognitive and clinical symptoms of Alzheimer’s disease. In contrast, levels of soluble forms of tau, such as CSF total tau and phosphorylated tau-181 and tau-217, increase prior to tau aggregation in Alzheimer’s disease, but these biomarkers do not measure the MTBR of tau. Thus, how CSF MTBR-tau is altered in Alzheimer’s disease remains unclear. In this study, we used sequential immunoprecipitation and chemical extraction methods followed by mass spectrometry to analyse MTBR-tau species in Alzheimer’s disease and control CSF. We quantified MTBR-tau-specific regions in the CSF and identified that species containing the region beginning at residue 243 were the most highly correlated with tau PET and cognitive measures. This finding suggests that CSF level of tau species containing the upstream region of MTBR may reflect changes in tau pathology that occur in Alzheimer’s disease and could serve as biomarkers to stage Alzheimer’s disease and track the development of tau-directed therapeutics.

Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer's Disease

2003 ◽  
pp. 601-607
Author(s):  
Jesús Ávila ◽  
José J. Lucas ◽  
Filip Lim ◽  
Mar Pérez ◽  
Félix Hernández ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Microtubule Binding

Smuggle tau through a secret(ory) pathway

2021 ◽  
Vol 478 (14) ◽  
pp. 2921-2925
Author(s):  
Hao Xu (徐昊)
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Recent Work ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Nerve Cells ◽  
Transmembrane Domains ◽  
Tau Pathology ◽  
Microtubule Binding

Secretion of misfolded tau, a microtubule-binding protein enriched in nerve cells, is linked to the progression of tau pathology. However, the molecular mechanisms underlying tau secretion are poorly understood. Recent work by Lee et al. [Biochemical J. (2021) 478: 1471–1484] demonstrated that the transmembrane domains of syntaxin6 and syntaxin8 could be exploited for tau release, setting a stage for testing a novel hypothesis that has profound implications in tauopathies (e.g. Alzheimer's disease, FTDP-17, and CBD/PSP) and other related neurodegenerative diseases. The present commentary highlights the importance and limitations of the study, and discusses opportunities and directions for future investigations.

scholarly journals A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease

2019 ◽  
Vol 12 ◽  
Author(s):  
Samuel Kakraba ◽  
Srinivas Ayyadevara ◽  
Narsimha Reddy Penthala ◽  
Meenakshisundaram Balasubramaniam ◽  
Akshatha Ganne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Protein Aggregation ◽  
Microtubule Binding

scholarly journals Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

2015 ◽  
Vol 36 (11) ◽  
pp. 4421-4437 ◽  
Author(s):  
Rik Ossenkoppele ◽  
Brendan I. Cohn-Sheehy ◽  
Renaud La Joie ◽  
Jacob W. Vogel ◽  
Christiane Möller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Stages

scholarly journals Can blood amyloid levels be used as a biomarker for Alzheimer’s disease?

2021 ◽  
Vol 7 (1) ◽  
pp. 17-25
Author(s):  
Yuan-Han Yang ◽  
Rocksy FV Situmeang ◽  
Paulus Anam Ong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Outcomes ◽  
Tau Protein ◽  
Clinical Settings ◽  
Access Methods ◽  
Clinical Applicability ◽  
Clinical Stages ◽  
Aging Populations ◽  
Amyloid Aβ

Alzheimer’s disease (AD) increasingly affects society due to aging populations. Even at pre‐clinical stages, earlier and accurate diagnoses are essential for optimal AD management and improved clinical outcomes. Biomarkers such as beta‐amyloid (Aβ) or tau protein in cerebrospinal fluid (CSF) have been used as reliable markers to distinguish AD from non‐AD, and predicting clinical outcomes, to attain these goals. However, given CSF access methods’ invasiveness, these biomarkers are not used extensively in clinical settings. Blood Aβ has been proposed as an alternative biomarker since it is less invasive than CSF; however, sampling heterogeneity has limited its clinical applicability. In this review, we investigated blood Aβ as a biomarker in AD and explored how Aβ can be facilitated as a viable biomarker for successful AD management.

scholarly journals Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer’s Disease

2020 ◽  
pp. 1-13
Author(s):  
Roos J. Jutten ◽  
Sietske A.M. Sikkes ◽  
Rebecca E. Amariglio ◽  
Rachel F. Buckley ◽  
Michael J. Properzi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Neuropsychological Tests ◽  
Clinical Stage ◽  
Word List ◽  
Time Interval ◽  
Cognitive Changes ◽  
Clinical Stages ◽  
Stage 1

Abstract Objective: Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework. Method: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. Results: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001). Conclusions: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.

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