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Blood-Based Biomarkers for Alzheimer’s Disease
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Blood-Based Biomarkers for Alzheimer’s Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 3819

Special Issue Editors

Dr. Constance Delaby

E-Mail Website
Guest Editor
1. LBPC-PPC, Université, Montpellier, CHU Montpellier, INM Inserm, Montpellier, France
2. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat autonoma de Barcelona, Barcelona, Spain
Interests: neurodegenerative diseases; clinical chemistry
Prof. Dr. Sylvain Lehmann

E-Mail Website
Guest Editor
LBPC-PPC, Universite, Montpellier, CHU Montpellier, INM Inserm, Montpellier, France
Interests: neurodegenerative diseases; clinical chemistry

Special Issue Information

Dear Colleagues,

The growing number of people with Alzheimer's disease (AD) represents a significant social and financial cost to the world population. The accurate detection of the earliest phase of preclinical AD is of major importance to the success of preventive and therapeutic strategies.

Early attempts to identify liquid biomarkers of neurological diseases are focused on cerebrospinal fluid (CSF) because of its anatomical proximity to the brain and its high content of neuronal proteins. The detection in CSF of biomarkers (such as amyloid peptides (Ab1-42 and Ab1-40), total tau protein and phospho-tau protein) has proven to be of great diagnostic value for AD, including in the prodromal stages. Additional biomarkers indicative of neurodegeneration (NfL), synaptic function (neurogranin, βSynuclein, etc.) glial response (GFAP, sTREM2, etc.) or inflammation (YKL-40, cytokines, etc.) also display interesting potential.

In recent years, several studies have shown that these brain proteins can also be detected in the blood, but their low concentration in this complex matrix complicates their use as biomarkers. In the last decade, the development of new ultrasensitive analytical approaches (such as immunoassays or quantitative mass spectrometry) has allowed a more robust measurement of these blood biomarkers. These assays hold promising potential for the early and minimally invasive detection of Alzheimer's disease, but also for the differential diagnosis of dementia and for the monitoring of the disease progression and response to treatment. The purpose of this Special Issue is therefore to provide an overview of molecular biology and chemistry studies and results related to the current blood-based biomarkers of AD.

Dr. Constance Delaby
Prof. Dr. Sylvain Lehmann
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Alzheimer’s disease
  • blood biomarkers
  • amyloid
  • tau proteins
  • neurodegeneration
  • diagnosis
  • prognosis
  • response to treatment
  • molecular research

Published Papers (3 papers)

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Research

17 pages, 1325 KiB  
Article
Definition of a Threshold for the Plasma Aβ42/Aβ40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia
by Lise Colmant, Emilien Boyer, Thomas Gerard, Kristel Sleegers, Renaud Lhommel, Adrian Ivanoiu, Philippe Lefèvre, Pascal Kienlen-Campard and Bernard Hanseeuw
Int. J. Mol. Sci. 2024, 25(2), 1173; https://doi.org/10.3390/ijms25021173 - 18 Jan 2024
Viewed by 1496
Abstract
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-positron emission tomography (PET) or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for [...] Read more.
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-positron emission tomography (PET) or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n = 88) and some volunteers (n = 66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden’s index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD. Full article
(This article belongs to the Special Issue Blood-Based Biomarkers for Alzheimer’s Disease)
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12 pages, 1041 KiB  
Article
Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum
by Sylvain Lehmann, Susanna Schraen-Maschke, Jean-Sébastien Vidal, Frédéric Blanc, Claire Paquet, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, Constance Delaby and Olivier Hanon
Int. J. Mol. Sci. 2023, 24(24), 17361; https://doi.org/10.3390/ijms242417361 - 11 Dec 2023
Viewed by 907
Abstract
Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer’s disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did [...] Read more.
Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer’s disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer’s diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer’s disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants’ conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients. Full article
(This article belongs to the Special Issue Blood-Based Biomarkers for Alzheimer’s Disease)
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12 pages, 1588 KiB  
Article
Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome
by Chung-Hsin Wu, Xun-Sheng Pan, Li-Yu Su and Shieh-Yueh Yang
Int. J. Mol. Sci. 2023, 24(18), 13771; https://doi.org/10.3390/ijms241813771 - 06 Sep 2023
Viewed by 1030
Abstract
The number of elderly dogs is increasing significantly worldwide, and many elderly dogs develop canine cognitive dysfunction syndrome (CCDS). CCDS is the canine analog of Alzheimer’s disease (AD) in humans. It is very important to develop techniques for detecting CDDS in dogs. Thus, [...] Read more.
The number of elderly dogs is increasing significantly worldwide, and many elderly dogs develop canine cognitive dysfunction syndrome (CCDS). CCDS is the canine analog of Alzheimer’s disease (AD) in humans. It is very important to develop techniques for detecting CDDS in dogs. Thus, we used the detection of neurofilament light chains (NfL) in plasma as a blood-based biomarker for the early diagnosis of canine Alzheimer’s disease using immunomagnetic reduction (IMR) technology by immobilizing NfL antibodies on magnetic nanoparticles. According to the 50-point CCDS rating scale, we divided 36 dogs into 15 with CCDS and 21 without the disease. The results of our IMR assay showed that the plasma NfL levels of dogs with CCDS were significantly increased compared to normal dogs (p < 0.01). By plasma biochemical analysis, we further confirmed that the liver and renal dysfunction biomarkers of dogs with CCDS were significantly elevated compared to normal dogs (p < 0.01–0.05). On the basis of our preliminary study, we propose that IMR technology could be an ideal biosensor for detecting plasma NfL for the early diagnosis of CCDS. Full article
(This article belongs to the Special Issue Blood-Based Biomarkers for Alzheimer’s Disease)
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