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Prof. Takashi Kudo

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Guest Editor

Department of Mental Health Promotion, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan
Interests: plasma biomarkers; neuron-derived extracellular vesicles; liquid biopsy

Dr. Shoshin Akamine

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Guest Editor Assistant

Division of Psychiatry, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan

Special Issue Information

Dear Colleagues,

Recently, the molecular mechanisms of dementia are gradually becoming clearer. Among them, for Alzheimer's disease (AD), the "amyloid cascade hypothesis" has been proposed and has been supported by many researchers. Based on this hypothesis, diagnostic biomarkers for AD have been established. The main ones are amyloid PET and the measurement of Aβ40, Aβ42, and phosphorylated tau in cerebrospinal fluid (CSF). However, amyloid PET is expensive, and CSF collection has invasive problems, leaving doubts about its clinical applicability. The amyloid hypothesis is also leading AD-modifying agents such as amyloid vaccine therapy to clinical use. Because it has been pointed out that such interventions cannot be expected to be effective unless they are performed very early in the disease, early diagnosis is becoming more important. Against this background, the establishment of blood biomarkers for AD that can be easily measured is an urgent issue.

On the other hand, clinical trials of these AD-modifying agents have been struggling, and questions have been raised as to whether the amyloid hypothesis is correct. Therefore, a paradigm shift may be necessary for the hypothesis of the molecular mechanisms of dementia.

In this Special Issue, we would like to introduce the molecular mechanisms of dementia, including the "amyloid cascade hypothesis," and introduce their application to biomarkers of dementia.

Prof. Takashi Kudo
Guest Editor

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Keywords

plasma
serum
phosphorylated tau
neurofilament L
Aβ40
Aβ42
extracellular vesicles
exosome

Published Papers (2 papers)

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Research

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13 pages, 8143 KiB

Open AccessArticle

Discovery of a Metabolic Signature Predisposing High Risk Patients with Mild Cognitive Impairment to Converting to Alzheimer’s Disease

by Yi-Long Huang, Chao-Hsiung Lin, Tsung-Hsien Tsai, Chen-Hua Huang, Jie-Ling Li, Liang-Kung Chen, Chun-Hsien Li, Ting-Fen Tsai and Pei-Ning Wang

Int. J. Mol. Sci. 2021, 22(20), 10903; https://doi.org/10.3390/ijms222010903 - 09 Oct 2021

Cited by 12 | Viewed by 2428

Abstract

Assessing dementia conversion in patients with mild cognitive impairment (MCI) remains challenging owing to pathological heterogeneity. While many MCI patients ultimately proceed to Alzheimer’s disease (AD), a subset of patients remain stable for various times. Our aim was to characterize the plasma metabolites of nineteen MCI patients proceeding to AD (P-MCI) and twenty-nine stable MCI (S-MCI) patients by untargeted metabolomics profiling. Alterations in the plasma metabolites between the P-MCI and S-MCI groups, as well as between the P-MCI and AD groups, were compared over the observation period. With the help of machine learning-based stratification, a 20-metabolite signature panel was identified that was associated with the presence and progression of AD. Furthermore, when the metabolic signature panel was used for classification of the three patient groups, this gave an accuracy of 73.5% using the panel. Moreover, when specifically classifying the P-MCI and S-MCI subjects, a fivefold cross-validation accuracy of 80.3% was obtained using the random forest model. Importantly, indole-3-propionic acid, a bacteria-generated metabolite from tryptophan, was identified as a predictor of AD progression, suggesting a role for gut microbiota in AD pathophysiology. Our study establishes a metabolite panel to assist in the stratification of MCI patients and to predict conversion to AD. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Dementia—Application to Its Biomarkers)

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Review

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23 pages, 323 KiB

Open AccessReview

Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment

by Tsuyoshi Nakai, Kiyofumi Yamada and Hiroyuki Mizoguchi

Int. J. Mol. Sci. 2021, 22(11), 5549; https://doi.org/10.3390/ijms22115549 - 24 May 2021

Cited by 20 | Viewed by 4620

Abstract

Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Dementia—Application to Its Biomarkers)

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