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Molecular Biomarkers and Precision Medicine for Alzheimer
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Molecular Biomarkers and Precision Medicine for Alzheimer

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Methodology, Drug and Device Discovery".

Deadline for manuscript submissions: closed (30 March 2022) | Viewed by 16614

Special Issue Editor

Dr. Valentina Bessi

E-Mail Website
Guest Editor
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy
Interests: neurodegeneration; cognitive neuroscience; PET/CT; molecular imaging; neuroimaging

Special Issue Information

Dear Colleagues,

The diagnosis of Alzheimer’s disease (AD) is particularly challenging in the prodromal stages, when neuropathological changes might be present but symptoms are still mild, and in atypical clinical presentations in which the differential diagnosis between AD and other neurodegenerative dementia could be difficult due to overlapping symptoms.

It is therefore particularly important to identify potential biomarkers that can be used in the early detection of AD, i.e., before clinical signs appear, as well as to distinguish between AD and other types of dementia.

In this Special Issue, the current knowledge as well as future perspectives on the role of biomarkers in screening and differential diagnosis of Alzheimer’s disease will be discussed.

In particular, papers investigating the role of current and future CSF and blood biomarkers, genetic factors involved in cognitive decline, and molecular imaging biomarkers are requested.

Prof. Valentina Bessi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biomarkers 
  • Alzheimer’s disease 
  • Dementia 
  • Neurodegeneration 
  • Brain 
  • Genetics

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Published Papers (5 papers)

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Research

14 pages, 1831 KiB  
Article
Alzheimer’s Disease CSF Biomarker Profiles in Idiopathic Normal Pressure Hydrocephalus
by Salvatore Mazzeo, Filippo Emiliani, Silvia Bagnoli, Sonia Padiglioni, Lorenzo Maria Del Re, Giulia Giacomucci, Juri Balestrini, Assunta Ingannato, Valentina Moschini, Carmen Morinelli, Giulia Galdo, Cristina Polito, Camilla Ferrari, Gastone Pansini, Alessandro Della Puppa, Sandro Sorbi, Benedetta Nacmias and Valentina Bessi
J. Pers. Med. 2022, 12(6), 935; https://doi.org/10.3390/jpm12060935 - 6 Jun 2022
Cited by 7 | Viewed by 2135
Abstract
Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ42 levels, comparable with Alzheimer’s Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ42 [...] Read more.
Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ42 levels, comparable with Alzheimer’s Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ42, Aβ42/Aβ40, p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ42 levels were not different between iNPH and AD, while Aβ42/Aβ40, p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ42/Aβ40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ42/Aβ40 had higher p-tau and t-tau than iNPH patients with negative Aβ42/Aβ40. Those iNPH patients who showed cognitive impairment had lower Aβ42/Aβ40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ42 with negative Aβ42/Aβ40, p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ42/Aβ40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology. Full article
(This article belongs to the Special Issue Molecular Biomarkers and Precision Medicine for Alzheimer)
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11 pages, 1565 KiB  
Article
Altered TIMP-3 Levels in the Cerebrospinal Fluid and Plasma of Patients with Alzheimer’s Disease
by Jung Hyun Park, Sun-Jung Cho, Chulman Jo, Moon Ho Park, Changsu Han, Eun-Joo Kim, Gi Yeong Huh and Young Ho Koh
J. Pers. Med. 2022, 12(5), 827; https://doi.org/10.3390/jpm12050827 - 19 May 2022
Cited by 7 | Viewed by 2293
Abstract
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aβ production and the pathophysiology of Aβ deposition in brains. However, studies on the amount of TIMP-3 in bodily fluids of [...] Read more.
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aβ production and the pathophysiology of Aβ deposition in brains. However, studies on the amount of TIMP-3 in bodily fluids of Alzheimer’s disease (AD) patients have not been conducted. Here, we investigated the relationship between fluid TIMP-3 levels and AD pathology. We first showed that the fluid levels of TIMP-3 were lower in AD dementia patients compared with in non-AD patients. ELISA results revealed that plasma levels of TIMP-3 in 65 patients with AD were significantly lower than those in 115 healthy control subjects and 71 mild cognitive impairment (MCI) subjects. Furthermore, we found that cerebrospinal fluid (CSF) level of TIMP-3 was decreased in AD compared with that in healthy control. These data suggest that fluid TIMP-3 levels negatively correlated with progress of cognitive decline. Collectively, our study suggests that alterations of fluid TIMP-3 levels might be associated with AD pathology. Full article
(This article belongs to the Special Issue Molecular Biomarkers and Precision Medicine for Alzheimer)
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18 pages, 1398 KiB  
Article
MicroRNA-Target Interaction Regulatory Network in Alzheimer’s Disease
by Aleksander Turk, Tanja Kunej and Borut Peterlin
J. Pers. Med. 2021, 11(12), 1275; https://doi.org/10.3390/jpm11121275 - 2 Dec 2021
Cited by 13 | Viewed by 3245
Abstract
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on [...] Read more.
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome. Full article
(This article belongs to the Special Issue Molecular Biomarkers and Precision Medicine for Alzheimer)
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14 pages, 9728 KiB  
Article
Systematic Search for Novel Circulating Biomarkers Associated with Extracellular Vesicles in Alzheimer’s Disease: Combining Literature Screening and Database Mining Approaches
by David Vogrinc, Katja Goričar, Tanja Kunej and Vita Dolžan
J. Pers. Med. 2021, 11(10), 946; https://doi.org/10.3390/jpm11100946 - 23 Sep 2021
Cited by 7 | Viewed by 2891
Abstract
miRNAs play an important role in neurodegenerative diseases. Many miRNA-target gene interactions (MTI) have been experimentally confirmed and associated with Alzheimer’s disease (AD). miRNAs may also be contained within extracellular vesicles (EVs), mediators of cellular communication and a potential source of circulating biomarkers [...] Read more.
miRNAs play an important role in neurodegenerative diseases. Many miRNA-target gene interactions (MTI) have been experimentally confirmed and associated with Alzheimer’s disease (AD). miRNAs may also be contained within extracellular vesicles (EVs), mediators of cellular communication and a potential source of circulating biomarkers in body fluids. Therefore, EV-associated miRNAs (EV-miRNAs) in peripheral blood could support earlier and less invasive AD diagnostics. We aimed to prioritize EV-related miRNA with AD-related genes and to identify the most promising candidates for novel AD biomarkers. A list of unique EV-miRNAs from the literature was combined with a known set of AD risk genes and enriched for MTI. Additionally, miRNAs associated with the AD phenotype were combined with all known target genes in MTI enrichment. Expression in different sample types was analyzed to identify AD-associated miRNAs with the greatest potential as AD circulating biomarkers. Four common MTI were observed between EV-miRNAs and AD-associated miRNAs: hsa-miR-375–APH1B, hsa-miR-107–CDC42SE2, hsa-miR-375–CELF2, and hsa-miR-107–IL6. An additional 61 out of 169 unique miRNAs (36.1%) and seven out of 84 unique MTI (8.3%), observed in the body fluids of AD patients, were proposed as very strong AD-circulating biomarker candidates. Our analysis summarized several potential novel AD biomarkers, but further studies are needed to evaluate their potential in clinical practice. Full article
(This article belongs to the Special Issue Molecular Biomarkers and Precision Medicine for Alzheimer)
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16 pages, 1970 KiB  
Article
A Conformation Variant of p53 Combined with Machine Learning Identifies Alzheimer Disease in Preclinical and Prodromal Stages
by Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo and Daniela Uberti
J. Pers. Med. 2021, 11(1), 14; https://doi.org/10.3390/jpm11010014 - 26 Dec 2020
Cited by 24 | Viewed by 5044
Abstract
Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease management. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise [...] Read more.
Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease management. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation recognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E epsilon-4 (APOEε4) and is able to predict AD likelihood risk in InveCe.Ab with an overall 86.67% agreement with clinical diagnosis. These algorithms also accurately classify (AUC = 0.92) Aβ+—amnestic Mild Cognitive Impairment (aMCI) patients who will develop AD in PharmaCog/E-ADNI, where subjects were stratified according to Cerebrospinal fluid (CSF) AD markers (Aβ42 and p-Tau). Results support U-p532D3A8+ plasma level as a promising additional candidate blood-based biomarker for AD. Full article
(This article belongs to the Special Issue Molecular Biomarkers and Precision Medicine for Alzheimer)
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