Biomarkers in Alzheimer disease: are we there yet?

Generoso, Jaqueline S.; Morales, Rodrigo; Barichello, Tatiana

doi:10.1590/1516-4446-2020-0013

Cited by 11 publications

(5 citation statements)

References 10 publications

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“…A β , tau, and P-tau are biomarkers of AD and have been explored as diagnostic markers in blood and cerebrospinal fluid [ 29 ]. In AD, A β fibrils polymerize into insoluble amyloid fibrils that aggregate into senile plaques, which activate kinases, leading to hyperphosphorylation of tau and its polymerization into insoluble neurofibrillary tangles.…”

Section: Discussionmentioning

confidence: 99%

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

et al. 2022

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Alzheimer’s disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb—Gastrodia elata—and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

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Section: Discussionmentioning

confidence: 99%

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

et al. 2022

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“…[ 1,2 ] Suitable methods used to diagnose an individual's predisposition toward neurological degeneration and dementia‐associated disorders through early biomarkers can bridge this gap. [ 3–5 ] The worldwide social and economic impact of Alzheimer's disease (AD) dictates the need for the timely invention of theranostics (therapeutics + diagnostics) for this disease. Continuous failure of anti‐AD drugs targeted to neurotransmitters and their interactions with toxic amyloid‐β (Aβ) peptides in clinical trials has brought the spotlight back to amyloidosis in AD.…”

Section: Introductionmentioning

confidence: 99%

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Sharma

Grandjean

Phillips

et al. 2021

Advanced NanoBiomed Research

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With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their later years. Endogenous proteins, such as the most abundant secreted protein in cerebrospinal fluid, lipocalin‐type prostaglandin d synthase (L‐PGDS), can bind the early toxic oligomers of amyloid β (Aβ) peptides implicated in AD and prevent their aggregation. Herein, the utility of L‐PGDS for detection of amyloids is demonstrated. L‐PGDS is conjugated with different iron‐oxide magnetic nanoparticles for contrast‐enhanced visualization using magnetic resonance imaging (MRI). These conjugates inhibit amyloid aggregation in vitro and improve viability in neuronal cells incubated with amyloid fibrils, showing a potential neuroprotective function. L‐PGDS‐ferritin conjugates, when administered intraventricularly, localize to AD‐associated amyloid‐rich regions in mice brain imaged using MRI and histological stains. As a proof‐of‐concept, it is demonstrated that L‐PGDS conjugates could reach the brain regions through non‐invasive intranasal administration. These conjugates are developed as the first entirely protein‐based nanoprobes for early detection of brain amyloids. The results of this study open a wider avenue for study of endogenous proteins as potential theranostics for AD.

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“…Many studies have conducted plasma proteomics analyses across the AD spectrum from cognitively normal (CN) to mild cognitively impaired to confirmed early and late-onset AD [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. The most widely used biomarkers in plasma are amyloid-beta 40 (Aβ 40 ) and 42 (Aβ 42 ) peptides [38,45,[65][66][67]. Other potential plasma protein biomarkers, a few of which have been validated within the same cohort [68] and few in independent cohorts [46,48,59,69,70], also exist.…”

Section: Introductionmentioning

confidence: 99%

Why Inclusion Matters for Alzheimer’s Disease Biomarker Discovery in Plasma

Khan

Desaire

López

et al. 2021

JAD

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Background: African American/Black adults have a disproportionate incidence of Alzheimer’s disease (AD) and are underrepresented in biomarker discovery efforts. Objective: This study aimed to identify potential diagnostic biomarkers for AD using a combination of proteomics and machine learning approaches in a cohort that included African American/Black adults. Methods: We conducted a discovery-based plasma proteomics study on plasma samples (N = 113) obtained from clinically diagnosed AD and cognitively normal adults that were self-reported African American/Black or non-Hispanic White. Sets of differentially-expressed proteins were then classified using a support vector machine (SVM) to identify biomarker candidates. Results: In total, 740 proteins were identified of which, 25 differentially-expressed proteins in AD came from comparisons within a single racial and ethnic background group. Six proteins were differentially-expressed in AD regardless of racial and ethnic background. Supervised classification by SVM yielded an area under the curve (AUC) of 0.91 and accuracy of 86%for differentiating AD in samples from non-Hispanic White adults when trained with differentially-expressed proteins unique to that group. However, the same model yielded an AUC of 0.49 and accuracy of 47%for differentiating AD in samples from African American/Black adults. Other covariates such as age, APOE4 status, sex, and years of education were found to improve the model mostly in the samples from non-Hispanic White adults for classifying AD. Conclusion: These results demonstrate the importance of study designs in AD biomarker discovery, which must include diverse racial and ethnic groups such as African American/Black adults to develop effective biomarkers.

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Biomarkers in Alzheimer disease: are we there yet?

Cited by 11 publications

References 10 publications

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Why Inclusion Matters for Alzheimer’s Disease Biomarker Discovery in Plasma

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