scholarly journals Amyloid-Targeting Drugs for the Treatment of Alzheimer Disease

2021 ◽  
Vol 39 (3) ◽  
pp. 134-140
Author(s):  
Ae Young Lee
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Drug Administration ◽  
Functional Ability ◽  
Amyloid Β ◽  
Symptomatic Improvement ◽  
Aβ Peptide ◽  
Common Cause ◽  
Disease Modifying ◽  
Disease Modifying Treatment

Alzheimer’s disease (AD) is the most common cause of dementia, characterized by cognitive impairment, neurobehavioral changes, and loss of functional ability. Current therapeutic options for AD are limited to medications that contribute to modest symptomatic improvement. The amyloid β (Aβ) peptide is central to the pathogenesis, so that immunotherapy targeting Aβ has been focused as a putative disease-modifying treatment for AD. In this review, I review the ongoing Aβ -directed immunotherapies, including aducanumab, which is the new AD medication since 2003 as well as the first disease-modifying treatment on the market approved by the Food and Drug Administration.

scholarly journals Current and Future Treatments in Alzheimer Disease: An Update

2020 ◽  
Vol 12 ◽  
pp. 117957352090739 ◽  
Author(s):  
Konstantina G Yiannopoulou ◽  
Sokratis G Papageorgiou
Keyword(s):  
Alzheimer Disease ◽  
Clinical Symptoms ◽  
Neurofibrillary Tangle ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Amyloid Β ◽  
Cell Therapies ◽  
Novel Biomarkers ◽  
Disease Modifying ◽  
Underlying Mechanisms

Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis

2012 ◽  
Vol 19 (5) ◽  
pp. 543-552 ◽  
Author(s):  
Kristin Augutis ◽  
Markus Axelsson ◽  
Erik Portelius ◽  
Gunnar Brinkmalm ◽  
Ulf Andreasson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Inflammatory Diseases ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Aβ Peptide ◽  
Aβ Peptides ◽  
App Metabolism ◽  
Disease Modifying

Background: Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. Objective: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. Methods: CSF samples from 87 MS patients (54 relapsing–remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1–2 years of treatment. Results: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. Conclusions: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.

First-level Neurocognitive Screening Tests and Their Application

2021 ◽  
Author(s):  
Francesco Salis
Keyword(s):  
Monoclonal Antibody ◽  
Drug Administration ◽  
Biomedical Research ◽  
Food And Drug Administration ◽  
Amyloid Β ◽  
Effective Therapy ◽  
Screening Tests ◽  
Screening Methods ◽  
Common Cause ◽  
The Brain

Finding an effective therapy able to slow Neurocognitive Disorder’s (NCD) progression represents an ambitious purpose of biomedical research. In June 2021, the Food and Drug Administration approved Aducanumab for the treatment of Alzheimer’s disease – the most common cause of dementia worldwide [1]. This drug is a monoclonal antibody that would be cause amyloid-β plaques reduction in the brain [2]. Whether its effectiveness will be confirmed or not, the fact remains that the patients that will benefit the most from any treatment are the ones suffering from mild NCD. Mild NCD is a clinically insidious and difficult-to-diagnose disorder, and consequently, the development and the spread of screening methods are necessary to early intercept these subjects.

scholarly journals The Role of Lysosomes in a Broad Disease-Modifying Approach Evaluated across Transgenic Mouse Models of Alzheimer’s Disease and Parkinson’s Disease and Models of Mild Cognitive Impairment

2019 ◽  
Vol 20 (18) ◽  
pp. 4432 ◽  
Author(s):  
Jeannie Hwang ◽  
Candice M. Estick ◽  
Uzoma S. Ikonne ◽  
David Butler ◽  
Morgan C. Pait ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Age Related ◽  
Disease Modifying

Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing. We investigated the role of lysosomes in Alzheimer’s disease (AD) and other age-related disorders, as well as in a strategy to compensate for lysosomal disturbances. Comprehensive immunostaining was used to analyze brains from wild-type mice vs. amyloid precursor protein/presenilin-1 (APP/PS1) mice that express mutant proteins linked to familial AD. Also, lysosomal modulation was evaluated for inducing synaptic and behavioral improvements in transgenic models of AD and Parkinson’s disease, and in models of mild cognitive impairment (MCI). Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration. Within neurons, lysosomes contain the amyloid β 42 (Aβ42) degradation product Aβ38, and this indicator of Aβ42 detoxification was augmented by Z-Phe-Ala-diazomethylketone (PADK; also known as ZFAD) as it enhanced the lysosomal hydrolase cathepsin B (CatB). PADK promoted Aβ42 colocalization with CatB in lysosomes that formed clusters in neurons, while reducing Aβ deposits as well. PADK also reduced amyloidogenic peptides and α-synuclein in correspondence with restored synaptic markers, and both synaptic and cognitive measures were improved in the APP/PS1 and MCI models. These findings indicate that lysosomal perturbation contributes to synaptic and cognitive decay, whereas safely enhancing protein clearance through modulated CatB ameliorates the compromised synapses and cognition, thus supporting early CatB upregulation as a disease-modifying therapy that may also slow the MCI to dementia continuum.

Cognitive symptoms of Alzheimer’s disease: clinical management and prevention

BMJ ◽  
2019 ◽  
pp. l6217 ◽  
Author(s):  
Elizabeth Joe ◽  
John M Ringman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Amyloid Cascade Hypothesis ◽  
Prodromal Ad ◽  
Disease Modifying ◽  
Medical Foods ◽  
Disease Modifying Treatment ◽  
Amyloid Cascade

ABSTRACTAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid β in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.

scholarly journals Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment

2015 ◽  
Vol 29 (3) ◽  
pp. 149-159 ◽  
Author(s):  
Jun Ku Chung ◽  
Eric Plitman ◽  
Shinichiro Nakajima ◽  
M. Mallar Chakravarty ◽  
Fernando Caravaggio ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Depressive Symptoms ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Amyloid Β

scholarly journals A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease

2014 ◽  
Vol 290 (4) ◽  
pp. 1966-1978 ◽  
Author(s):  
Yukiko Hori ◽  
Shuko Takeda ◽  
Hansang Cho ◽  
Susanne Wegmann ◽  
Timothy M. Shoup ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Drug Administration ◽  
Therapeutic Agent ◽  
Food And Drug Administration ◽  
Amyloid Β ◽  
Transgenic Model ◽  
The Brain

scholarly journals Genetic Dissection of Alzheimer’s Disease Using Drosophila Models

2020 ◽  
Vol 21 (3) ◽  
pp. 884 ◽  
Author(s):  
Youngjae Jeon ◽  
Jae Ha Lee ◽  
Byoungyun Choi ◽  
So-Yoon Won ◽  
Kyoung Sang Cho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Amyloid Β ◽  
Genetic Dissection ◽  
Abnormal Accumulation ◽  
Disease Modifying ◽  
Disease Modifying Treatment ◽  
Drosophila Models

Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment. Drosophila, as the most advanced genetic model, has been used to explore the molecular mechanisms of AD in the last few decades. Here, we introduce Drosophila AD models based on human Aβ and summarize the results of their genetic dissection. We also discuss the utility of functional genomics using the Drosophila system in the search for AD-associated molecular mechanisms in the post-genomic era.

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