Prognosis of Biomarker of Alzheimer’s Disease in the Function of the Retina and Secondary Molecular Structure Variation of the Retina and BrainRead the full article
International Journal of Alzheimer’s Disease publishes original research articles and review articles in all areas of Alzheimer's disease.
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A Comprehensive Investigation of the Potential Role of Lipoproteins and Metabolite Profile as Biomarkers of Alzheimer’s Disease Compared to the Known CSF Biomarkers
Introduction. While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer’s disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including Aβ-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Method. Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender. Results. A total number of 251 AD subjects were included, among whom 71 subjects were negative for the Apo-E ε4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of Aβ-42 () and phenylalanine (), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers. Conclusion. Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in Apo-E ε4 positive and negative groups, which reminds the role of Apo-E gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology.
Cyclic Glycine-Proline Improves Memory and Reduces Amyloid Plaque Load in APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease
Alzheimer’s disease (AD) is a neurodegenerative condition that is pathologically characterized by the presence of amyloid plaques and neurofibrillary tangles. Animal models of AD have been useful in understanding the disease process and in investigating the effects of compounds on pathology and behavior. APP/PS1 mice develop amyloid plaques and show memory impairment. Cyclic glycine-proline (cGP) is a cyclic dipeptide that is likely produced from a tripeptide, glycine-proline-glutamate, which itself is generated after proteolytic cleavage of insulin-like growth factor-1. Here, we show that cGP improves spatial memory and reduces amyloid plaque burden in APP/PS1 mice. The results thus suggest that cGP could potentially provide beneficial effects in AD.
CSF-Targeted Proteomics Indicate Amyloid-Beta Ratios in Patients with Alzheimer’s Dementia Spectrum
Background. According to recent studies, amyloid-β (Aβ) isoforms as cerebrospinal fluid (CSF) biomarkers have remarkable predictive value for cognitive decline in the early stages of Alzheimer’s disease (AD). Herein, we aimed to investigate the correlations between several targeted proteomics in CSF samples with Aβ ratios and cognitive scores in patients in AD spectrum to search for potential early diagnostic utility. Methods. A total of 719 participants were found eligible for inclusion. Patients were then categorized into cognitively normal (CN), mild cognitive impairment (MCI), and AD and underwent an assessment of Aβ and proteomics. Clinical Dementia Rating (CDR), Alzheimer’s Disease Assessment Scale (ADAS), and Mini Mental State Exam (MMSE) were used for further cognitive assessment. The Aβ42, Aβ42/Aβ40, and Aβ42/38 ratios were considered as means of comparison to identify those peptides corresponding significantly to these established biomarkers and cognitive scores. The diagnostic utility of the IASNTQSR, VAELEDEK, VVSSIEQK, GDSVVYGLR, EPVAGDAVPGPK, and QETLPSK was assessed. Results. All investigated peptides corresponded significantly to Aβ42 in controls. In those with MCI, VAELEDEK and EPVAGDAVPGPK were significantly correlated with Aβ42 ( value < 0.001). Additionally, IASNTQSR, VVSSIEQK, GDSVVYGLR, and QETLPSK were significantly correlated with Aβ42/Aβ40 and Aβ42/38 ( value < 0.001) in this group. This group of peptides similarly corresponded to Aβ ratios in those with AD. Eventually, IASNTQSR, VAELEDEK, and VVSSIEQK were significantly associated with CDR, ADAS-11, and ADAS-13, particularly in MCI group. Conclusion. Our research suggests potential early diagnostic and prognostic utilities for certain peptides extracted from CSF-targeted proteomics research. The ethical approval of ADNI is available at ClinicalTrials.gov with Identifier: NCT00106899.
Trends in Healthcare Resource Use Preceding Diagnosis of Alzheimer’s Disease Dementia
Introduction. An Alzheimer’s disease (AD) dementia diagnosis is often preceded by an extended period of cognitive decline. Few studies have examined healthcare resource use (HRU) during an extended period before AD dementia diagnosis. Methods. In a historical claims-based cohort study, propensity score-matched cohorts of patients with and without AD dementia were observed for a 5-year prediagnosis period and a 1-year postdiagnosis period. Demographics, clinical characteristics, and HRU were compared between groups. Results. Individuals in the AD dementia group displayed a greater level of medical complexity in the year before diagnosis of AD dementia relative to those in the matched cohort. Both all-cause and AD dementia complication-related HRU increased gradually, with a marked spike at the time of initial AD dementia diagnosis. Discussion. Further research into the natural history of patients with AD dementia is necessary to improve identification of early AD and to better understand its broader impact.
Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAβ): A Plasma-Based Biomarker Differentiates Alzheimer’s Disease from Other Etiologies of Dementia
With emerging amyloid therapies, documentation of the patient’s amyloid status to confirm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a noninvasive blood-based biomarker utilized to measure Aβ oligomerization tendency. We determined the difference in MDS-OAβ ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer’s disease (AD), (c) non-AD, and (d) mixed Alzheimer’s disease-Vascular dementia (AD-VaD). MDS-OAβ level was not significantly different between AD and mixed AD-VaD, but both groups were significantly different from the NCI/SCI and from the non-AD group. An MDS-OAβ level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD).
Aducanumab Therapy to Treat Alzheimer’s Disease: A Narrative Review
Background. Aducanumab, a new monoclonal antibody that targets β-amyloid aggregates, has been granted conditional approval by the U.S. FDA for treatment of mild Alzheimer’s disease (AD). The approval of this drug without a confirmed significant clinical impact has resulted in several debates. Objective. In this narrative review, aducanumab approval-related controversy, the drug’s pharmacokinetics and pharmacodynamic characteristics, evidence from the efficacy and safety trials of aducanumab, implications of the drug approval, and the future directions in the management of patients with AD are summarized. Methods. Using relevant keywords, Google Scholar, Web of Science, and MEDLINE databases and manufacturer’s website were searched. Results. Infusion of aducanumab at a higher dose resulted in a modest slowing of cognitive decline among patients with mild cognitive impairment or early-onset AD dementia. The drug however can cause amyloid-related imaging abnormalities. Due to modest impact on cognition, the use of this drug by patients with AD will most likely be limited. The manufacturer is required to run an extended phase IIIb trial to verify the benefit of this drug. Access to therapy requires a careful selection of patients and periodic monitoring to ensure the optimal use of the drug. Conclusion. Despite the limitations, aducanumab is the first disease-modifying therapy approved for the treatment of AD. Aducanumab addresses a part of the pathogenesis of AD; therefore, drugs that can act on multiple targets are needed. In addition, the search for preventive strategies, validated plasma-based assays, and newer drugs for AD, which are effective, safe, convenient, and affordable, is vital.