Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease

Cho, Hyung Joon; Schulz, Philip; Venkataraman, Lalitha; Caselli, Richard J.; Sierks, Michael R.

doi:10.3390/ijms232415670

Cited by 8 publications

(3 citation statements)

References 61 publications

(104 reference statements)

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“…Moreover, these recent studies pointed to plasma p-Tau181 and other hyperphosphorylated Tau (p-Tau231, p-Tau217) as the most sensitive plasma biomarkers for AD diagnosis [ 18 , 19 ], even in the early stages [ 20 , 21 ]. In general, individual plasma biomarkers have shown good accuracy for AD diagnosis, which could be improved by the simultaneous combination of some plasma biomarkers [ 22 , 23 , 24 , 25 ]. The neurofilament light chain (NfL) is another molecule that has been analyzed in the context of AD as a progression biomarker [ 26 ] or predictor for dementia, even more helpful in other pathologies, such as FTLD [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Álvarez-Sánchez

Peña-Bautista²,

Ferré-González³

et al. 2023

IJMS

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Alzheimer’s disease (AD) is the primary type of dementia, followed by frontotemporal lobar degeneration (FTLD). They share some clinical characteristics, mainly at the early stages. So, the identification of early, specific, and minimally invasive biomarkers is required. In this study, some plasma biomarkers (Amyloid β42, p-Tau181, t-Tau, neurofilament light (NfL), TAR DNA-binding protein 43 (TDP-43)) were determined by single molecule array technology (SIMOA®) in control subjects (n = 22), mild cognitive impairment due to AD (MCI-AD, n = 33), mild dementia due to AD (n = 12), and FTLD (n = 11) patients. The correlations between plasma and cerebrospinal fluid (CSF) levels and the accuracy of plasma biomarkers for AD early diagnosis and discriminating from FTLD were analyzed. As result, plasma p-Tau181 and NfL levels correlated with the corresponding CSF levels. Additionally, plasma p-Tau181 showed good accuracy for distinguishing between the controls and AD, as well as discriminating between AD and FTLD. Moreover, plasma NfL could discriminate dementia-AD vs. controls, FTLD vs. controls, and MCI-AD vs. dementia-AD. Therefore, the determination of these biomarkers in plasma is potentially helpful in AD spectrum diagnosis, but also discriminating from FTLD. In addition, the accessibility of these potential early and specific biomarkers may be useful for AD screening protocols in the future.

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Section: Introductionmentioning

confidence: 99%

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Álvarez-Sánchez

Peña-Bautista²,

Ferré-González³

et al. 2023

IJMS

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“…For example, it has been found that direct injection of glutamate into rat insula with no other intervention led to IENFD reductions, highlighting the possibility that imbalances in CNS excitatory neurotransmitters may play a role in IENFD [31]. Alternatively, a "top-around" effect in which signaling molecules or factors are released due to CNS injury could secondarily impact peripheral fibers through the bloodstream or other nonneural pathways [32][33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Thomas

Enders

Kaiser

et al. 2023

Preprint

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Background: Intraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique. Methods: We conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5). Results: We analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 74 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of -47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of -31.6 % and -34.7% respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents. Interpretation: Reduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

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“…The combination of several plasma biomarkers has demonstrated improved accuracy for AD diagnosis compared to individual ones, which also showed good accuracy [ 70 , 71 , 72 , 73 ]. It has been established that CSF p-tau levels increase while CSF Aβ levels decrease in AD [ 74 , 75 , 76 ]; the plasma ratio Aβ42/Aβ40 and p-tau181 protein can distinguish between AD and a healthy state [ 77 , 78 , 79 , 80 ].…”

Section: Current Biomarkers For the Diagnosis Of Alzheimer’s Disease ...mentioning

confidence: 99%

Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Taneva,

Todinova,

Andreeva

2023

IJMS

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Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today’s society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs—Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.

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Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease

Cited by 8 publications

References 61 publications

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

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