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Repurposed agents in the Alzheimer’s disease drug development pipeline
Treatments are needed to address the growing prevalence of Alzheimer’s disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the phar...Alzheimer's Research & Therapy 2020 12:98Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease
Alzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predic...Alzheimer's Research & Therapy 2020 12:97Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease
The amyloid precursor protein (APP) is a transmembrane glycoprotein that undergoes alternative proteolytic processing. Its processing through the amyloidogenic pathway originates a large sAPPβ ectodomain fragm...Alzheimer's Research & Therapy 2020 12:96Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval
The body of evidence suggesting a causative, initiating role of beta amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD) is substantial. Yet, only a few anti-amyloid agents have shown meaningful effic...Alzheimer's Research & Therapy 2020 12:95Estimating the potential for dementia prevention through modifiable risk factors elimination in the real-world setting: a population-based study
Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not cons...Alzheimer's Research & Therapy 2020 12:94Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis
A substantial number of patients clinically diagnosed with Alzheimer’s disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (...Alzheimer's Research & Therapy 2020 12:93Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions
Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer’s disease (AD). The objective of this study was to examine the association of sele...Alzheimer's Research & Therapy 2020 12:92The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer’s disease
Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer’s disease, although its efficacy is still under debate. We aimed to investigate th...Alzheimer's Research & Therapy 2020 12:91Assessing what matters most to patients with or at risk for Alzheimer’s and care partners: a qualitative study evaluating symptoms, impacts, and outcomes
The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer’s disease (AD) and...Alzheimer's Research & Therapy 2020 12:90Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease
Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive ...Alzheimer's Research & Therapy 2020 12:89CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease
The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein ki...Alzheimer's Research & Therapy 2020 12:88Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through RNA sequencing analysis
With demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer’s disease (AD) is the most common cause of dementia, and no curative treatment is availabl...Alzheimer's Research & Therapy 2020 12:87The role of interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease
The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association ...Alzheimer's Research & Therapy 2020 12:86Cardiovascular risk factors indirectly affect acute post-stroke cognition through stroke severity and prior cognitive impairment: a moderated mediation analysis
Cognitive impairment is an important consequence of stroke and transient ischaemic attack, but its determinants are not fully understood. Simple univariable or multivariable models have not shown clinical util...Alzheimer's Research & Therapy 2020 12:85Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration
Disturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects ...Alzheimer's Research & Therapy 2020 12:84CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation
Recently, several studies suggested potential involvements of α-synuclein in Alzheimer’s disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD pati...Alzheimer's Research & Therapy 2020 12:83Quantitative EEG as a biomarker in mild cognitive impairment with Lewy bodies
To investigate using quantitative EEG the (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer’s disease (MCI-AD) and (2) its utility as a potential ...Alzheimer's Research & Therapy 2020 12:82One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case “for” and “against”
Recently, it has been suggested that up to a third of the dementia cases might be preventable. While prevention is always better than cure, this is particularly important in the field of dementia, as current i...Alzheimer's Research & Therapy 2020 12:81Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40
Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid β-protein (Aβ) and the microtubule-associated protein, tau, and has been genetically linked to late-onset Alzheimer disease (AD). Here,...Alzheimer's Research & Therapy 2020 12:80The insula, a grey matter of tastes: a volumetric MRI study in dementia with Lewy bodies
Despite the growing number of discoveries during the past decades about its functions, the insula remains a mysterious ‘island’. In addition to its involvement in basic functions such as gustation and interoce...Alzheimer's Research & Therapy 2020 12:79Community memory screening as a strategy for recruiting older adults into Alzheimer’s disease research
Growing awareness of Alzheimer’s disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memor...Alzheimer's Research & Therapy 2020 12:78Imaging the aging brain: study design and baseline findings of the SENIOR cohort
Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into...Alzheimer's Research & Therapy 2020 12:77The short-term effects of sedentary behaviour on cerebral hemodynamics and cognitive performance in older adults: a cross-over design on the potential impact of mental and/or physical activity
Sedentary behaviour might be a potential risk factor for cognitive decline. However, the short-term effects of sedentary behaviour on (cerebro) vascular and cognitive performance in older people are unknown.Alzheimer's Research & Therapy 2020 12:76Diverse proteins aggregate in mild cognitive impairment and Alzheimer’s disease brain
All cells accumulate insoluble protein aggregates throughout their lifespan. While many studies have characterized the canonical disease-associated protein aggregates, such as those associated with amyloid pla...Alzheimer's Research & Therapy 2020 12:75The dynamics of biomarkers across the clinical spectrum of Alzheimer’s disease
Quantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer’s disease (AD) will provide a template for understanding the underlying aetiology of the cl...Alzheimer's Research & Therapy 2020 12:74Optical coherence tomography angiography as a potential screening tool for cerebral small vessel diseases
The retina and the brain share anatomic, embryologic, and physiologic characteristics. Therefore, retinal imaging in patients with brain disorders has been of significant interest. Using optical coherence tomo...Alzheimer's Research & Therapy 2020 12:73Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology
Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the study was to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN...Alzheimer's Research & Therapy 2020 12:72Correction to: Relevance of biomarkers across different neurodegenerative diseases
An amendment to this paper has been published and can be accessed via the original article.Alzheimer's Research & Therapy 2020 12:71The original article was published in Alzheimer's Research & Therapy 2020 12:56Young blood plasma reduces Alzheimer’s disease-like brain pathologies and ameliorates cognitive impairment in 3×Tg-AD mice
Recent studies indicated that circulatory factors in blood plasma from young animals can reactivate neurogenesis, restore synaptic plasticity, and improve cognitive function in aged animals. Here, we investiga...Alzheimer's Research & Therapy 2020 12:70Immediate and long-term consequences of COVID-19 infections for the development of neurological disease
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, les...Alzheimer's Research & Therapy 2020 12:69Reproducibility of EEG functional connectivity in Alzheimer’s disease
Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer’s disease (AD) compared to healthy subjects, there is no general consensus on the methodo...Alzheimer's Research & Therapy 2020 12:68- Alzheimer's Research & Therapy 2020 12:67
The Alzheimer’s Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer’s disease
There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer’s disease (AD) treatment trials. We reported previously a composite cognitive...Alzheimer's Research & Therapy 2020 12:66APOE ε4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer’s disease
Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer’s disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprote...Alzheimer's Research & Therapy 2020 12:65Testing whether the progression of Alzheimer’s disease changes with the year of publication, additional design, and geographical area: a modeling analysis of literature aggregate data
Our objectives were to develop a disease progression model for cognitive decline in Alzheimer’s disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on tri...Alzheimer's Research & Therapy 2020 12:64Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission
Alzheimer’s disease (AD) is the most common form of age-related neurodegenerative diseases. Cerebral deposition of Aβ peptides, especially Aβ42, is considered the major neuropathological hallmark of AD and the...Alzheimer's Research & Therapy 2020 12:63Physical exercise during exposure to 40-Hz light flicker improves cognitive functions in the 3xTg mouse model of Alzheimer’s disease
Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aβ) by stabilizing gamma oscillation. We examined ...Alzheimer's Research & Therapy 2020 12:62γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not
γ-Secretase is a multiprotein protease that cleaves amyloid protein precursor (APP) and other type I transmembrane proteins. It has two catalytic subunits, presenilins 1 and 2 (PS1 and 2). In our previous repo...Alzheimer's Research & Therapy 2020 12:61Is it time to use real-world data from primary care in Alzheimer’s disease?
The analysis of real-world data in clinical research is rising, but its use to study dementia subtypes has been hardly addressed. We hypothesized that real-world data might be a powerful tool to update AD epid...Alzheimer's Research & Therapy 2020 12:60Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this...Alzheimer's Research & Therapy 2020 12:59Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer’s disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study
Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD).Alzheimer's Research & Therapy 2020 12:58The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer’s disease
Lack of awareness of cognitive decline (ACD) has been described at the preclinical and prodromal stages of Alzheimer’s disease (AD). In this study, we introduced a meta-memory ratio (MMR) and explored how it i...Alzheimer's Research & Therapy 2020 12:57Relevance of biomarkers across different neurodegenerative diseases
The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and incre...Alzheimer's Research & Therapy 2020 12:56The Correction to this article has been published in Alzheimer's Research & Therapy 2020 12:71Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia
Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequen...Alzheimer's Research & Therapy 2020 12:55Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles
The contributions of brain intercellular communication mechanisms, specifically extracellular vesicles (EV), to the progression of Alzheimer’s disease (AD) remain poorly understood.Alzheimer's Research & Therapy 2020 12:54Correction to: Sleep dysregulation, memory impairment, and CSF biomarkers during different levels of neurocognitive functioning in Alzheimer’s disease course
An amendment to this paper has been published and can be accessed via the original article.Alzheimer's Research & Therapy 2020 12:53The original article was published in Alzheimer's Research & Therapy 2020 12:5Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea
Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea.Alzheimer's Research & Therapy 2020 12:52The cholinergic system in subtypes of Alzheimer’s disease: an in vivo longitudinal MRI study
The heterogeneity within Alzheimer’s disease (AD) seriously challenges the development of disease-modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subt...Alzheimer's Research & Therapy 2020 12:51The combined effects of microglia activation and brain glucose hypometabolism in early-onset Alzheimer’s disease
Early-onset Alzheimer’s disease (EOAD) is characterized by young age of onset (< 65 years), severe neurodegeneration, and rapid disease progression, thus differing significantly from typical late-onset Alzheim...Alzheimer's Research & Therapy 2020 12:50Imaging biomarkers in neurodegeneration: current and future practices
There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigati...Alzheimer's Research & Therapy 2020 12:49
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