scholarly journals Use of eye biomarkers in pre-clinical diagnosis of Alzheimer’s Disease

2021 ◽  
Author(s):  
Luísa França de Faria ◽  
Fernanda Roberti Gil de Paula ◽  
Gabriel Roncalli Soalheiro Prado Alves ◽  
Luiz Filipe de Oliveira Braga ◽  
Lilian Caiafa Ferreira Machado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Ocular Blood Flow ◽  
Unknown Etiology ◽  
Disease Biomarkers ◽  
Non Invasive ◽  
Amyloid Aβ ◽  
Eye Exams ◽  
Detection Of Biomarkers

Background: Alzheimer’s disease (AD) has an unknown etiology, but the main pathophysiological hypothesis consists of the accumulation of extracellular beta- amyloid (Aβ) plaques and the formation of intracellular neurofibrillary tangles of phosphorylated tau1,2. As brain changes follow the appearance of clinical symptoms, there is a difficulty in making the diagnosis and early treatment3,4. The detection of biomarkers in the retina guaranteed the preclinical diagnosis of AD, in an efficient and economical way5. Objectives: To highlight the application of ocular biomarkers in the early diagnosis of AD. Methods: This is a narrative review with search in the sources PubMed, Cochrane and TripDatabase using descriptors: “Alzheimer Disease”, “Biomarkers” and “Retina”. Seven articles were used, published from 2017 to 2021. Results: In patients with pre-clinical AD, accumulation of Aβ was detected with the formation of specifically smaller retinal plaques when compared to brain plaques, but quantitatively equivalent to the load of this protein in the brain and the severity of this pathology6. Thus, associated with the great advance in retinal imaging exams, AD can be diagnosed early by analyzing the structure of the retina and ocular blood flow in a non-invasive and efficient manner5,7. Instruments and systems for conducting eye exams, such as optical coherence tomography and retinography, are increasingly present in medical services, which makes it possible to carry out regular and constant tests in the population1,5. Conclusions: Further studies are required to verify the long- term application of ocular biomarkers in medical practice.

scholarly journals Biomarkers in Alzheimer’s disease

2021 ◽  
Author(s):  
Larissa Maria de Paula Rebouças da Costa ◽  
Gabriel de Souza Torres ◽  
Kauan Alves Sousa Madruga ◽  
Poliana Rafaela dos Santos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Low Cost ◽  
Meta Analysis ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Blood Tests ◽  
Pubmed Database ◽  
Amyloid Aβ ◽  
Phosphorylated Tau Protein

Background: Alzheimer’s disease (AD) is the most common cause of dementia and cognitive dysfunction in old ages. AD is characterised by beta- amyloid (Aβ) plaques and neurofibrillary tangles of the hyper-phosphorylated Tau protein. It has an extensive preclinical stage, which emphasizes the importance of the biological components related to an early diagnostic: biomarkers. Objectives: After critical analysis of the selected literature, this review has the goal of describing the main biomarkers in AD and discussing different ways of detecting it. Methods: This review was elaborated after a literature review in the PubMed database, with 15 articles published between 2016 and 2021. The keywords were used with the boolean operator “AND”. Articles of meta-analysis, review and systematic review were selected. Results: It was found central biomarkers for the AD diagnostic, such as Tau and Aβ. The following tests were used: CSF puncture; blood tests; neuroimaging; saliva and mucosa samples. Aβ and Tau can be collected by CSF or PET-TC. Conclusions: Biomarkers play an important role in early AD diagnostic, even with limitations in the tests. The CSF and PET-TC are expensive methods, only used in atypical cases of AD. Reliable blood tests remain in development. In conclusion, there’s the need for more studies about alternative diagnostic tests, that are non-invasive and have low cost. Those developments can be beneficial for health plans, helping early diagnosis of AD.

scholarly journals P4-196: ANALYSES OF URINE FATTY ACIDS IN PURSUIT OF NON-INVASIVE PRE-CLINICAL ALZHEIMER'S DISEASE BIOMARKERS

2019 ◽  
Vol 15 ◽  
pp. P1352-P1352
Author(s):  
Alfred N. Fonteh ◽  
Michael Kwong ◽  
Hannah Chew ◽  
Katherine Castor ◽  
Michael G. Harrington
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Disease Biomarkers ◽  
Non Invasive

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

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