Alzheimer's Research & Therapy
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Pay attention to the basal ganglia: a volumetric study in early dementia with Lewy bodies
Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whe...Alzheimer's Research & Therapy 2019 11:108Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice
Alzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive ...Alzheimer's Research & Therapy 2019 11:107Rescue of cognitive deficits in APP/PS1 mice by accelerating the aggregation of β-amyloid peptide
Brain amyloid deposition is one of the main pathological characteristics of Alzheimer’s disease (AD). Soluble oligomers formed during the process that causes β-amyloid (Aβ) to aggregate into plaques are consid...Alzheimer's Research & Therapy 2019 11:106CSF synaptic protein concentrations are raised in those with atypical Alzheimer’s disease but not frontotemporal dementia
Increased CSF levels of a number of synaptic markers have been reported in Alzheimer’s disease (AD), but little is known about their concentrations in frontotemporal dementia (FTD). We investigated this in thr...Alzheimer's Research & Therapy 2019 11:105HHV-6A infection induces amyloid-beta expression and activation of microglial cells
The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-be...Alzheimer's Research & Therapy 2019 11:104ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease
Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we ...Alzheimer's Research & Therapy 2019 11:103EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease
EphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer’s disease (AD), characterized by synapse dysfun...Alzheimer's Research & Therapy 2019 11:102Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis
We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR...Alzheimer's Research & Therapy 2019 11:101PET and CSF amyloid-β status are differently predicted by patient features: information from discordant cases
Amyloid-β PET and CSF Aβ42 yield discordant results in 10–20% of memory clinic patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic, and imaging feature...Alzheimer's Research & Therapy 2019 11:100Progression to dementia in memory clinic patients with mild cognitive impairment and normal β-amyloid
Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer’s disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within t...Alzheimer's Research & Therapy 2019 11:99Effects of functional tasks exercise on cognitive functions of older adults with mild cognitive impairment: a randomized controlled pilot trial
Dementia has been presenting an imminent public health challenge worldwide. Studies have shown a combination of cognitive and physical trainings may have synergistic value for improving cognitive functions. Da...Alzheimer's Research & Therapy 2019 11:98Characterization of the selective in vitro and in vivo binding properties of crenezumab to oligomeric Aβ
Accumulation of amyloid β (Aβ) in the brain is proposed as a cause of Alzheimer’s disease (AD), with Aβ oligomers hypothesized to be the primary mediators of neurotoxicity. Crenezumab is a humanized immunoglob...Alzheimer's Research & Therapy 2019 11:97Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer’s disease, supportive biomarker information is necessary. This study was aimed to investigate the association...Alzheimer's Research & Therapy 2019 11:96Transcranial magnetic stimulation and amyloid markers in mild cognitive impairment: impact on diagnostic confidence and diagnostic accuracy
The development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments ...Alzheimer's Research & Therapy 2019 11:95Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers
Results from recent clinical studies suggest that cerebrospinal fluid (CSF) biomarkers that are indicative of Alzheimer’s disease (AD) can be replicated in blood, e.g. amyloid-beta peptides (Aβ42 and Aβ40) and ne...Alzheimer's Research & Therapy 2019 11:94Systemic and central nervous system metabolic alterations in Alzheimer’s disease
Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer’s disease (AD) on both the systemic and c...Alzheimer's Research & Therapy 2019 11:93Study partner types and prediction of cognitive performance: implications to preclinical Alzheimer’s trials
Alzheimer’s disease (AD) clinical trials require enrollment of a participant and a study partner, whose role includes assessing participant cognitive and functional performance. AD trials now investigate early...Alzheimer's Research & Therapy 2019 11:92Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer’s disease
Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possib...Alzheimer's Research & Therapy 2019 11:91Retinal thinning of inner sub-layers is associated with cortical atrophy in a mouse model of Alzheimer’s disease: a longitudinal multimodal in vivo study
It has been claimed that the retina can be used as a window to study brain disorders. However, concerning Alzheimer’s disease (AD), it still remains controversial whether changes occurring in the brain and ret...Alzheimer's Research & Therapy 2019 11:90Association between increased levels of amyloid-β oligomers in plasma and episodic memory loss in Alzheimer’s disease
The objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) bet...Alzheimer's Research & Therapy 2019 11:89Age-dependent emergence of neurophysiological and behavioral abnormalities in progranulin-deficient mice
Loss-of-function mutations in the progranulin gene cause frontotemporal dementia, a genetic, heterogeneous neurodegenerative disorder. Progranulin deficiency leads to extensive neuronal loss in the frontal and...Alzheimer's Research & Therapy 2019 11:88Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer’s disease
Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physi...Alzheimer's Research & Therapy 2019 11:87Amyloid β-protein oligomers promote the uptake of tau fibril seeds potentiating intracellular tau aggregation
Repeated failure of drug candidates targeting Alzheimer’s disease (AD) in clinical trials likely stems from a lack of understanding of the molecular mechanisms underlying AD pathogenesis. Recent research has h...Alzheimer's Research & Therapy 2019 11:86Participant and study partner prediction and identification of cognitive impairment in preclinical Alzheimer’s disease: study partner vs. participant accuracy
Preclinical Alzheimer’s disease (AD) clinical trials require participants to enroll with a study partner, a person who can attend visits and report changes in the participant’s cognitive ability. Whether study...Alzheimer's Research & Therapy 2019 11:85Testing the 2018 NIA-AA research framework in a retrospective large cohort of patients with cognitive impairment: from biological biomarkers to clinical syndromes
According to the 2018 NIA-AA research framework, Alzheimer’s disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both a...Alzheimer's Research & Therapy 2019 11:84Amyloid-β peptides in cerebrospinal fluid of patients with dementia with Lewy bodies
One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-β (Aβ) metabolism in dementia...Alzheimer's Research & Therapy 2019 11:83Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer’s and Parkinson’s disease
Increasing evidence implicates dysfunctional proteostasis and the involvement of the autophagic and endo-lysosomal system and the ubiquitin-proteasome system in neurodegenerative diseases. In Alzheimer’s disea...Alzheimer's Research & Therapy 2019 11:82CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (...Alzheimer's Research & Therapy 2019 11:81Visual hallucinations in Alzheimer's disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas
Up to 20% of patients with AD experience hallucinations. The pathological substrate is not known. Visual hallucinations (VH) are more common in dementia with Lewy bodies (DLB). In autopsy studies, up to 60% of...Alzheimer's Research & Therapy 2019 11:80Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies
Very little is known for the direction or causality of the relationship between lifetime sleep experiences and in vivo Alzheimer’s disease (AD) pathologies. This study aimed to examine the relationship between...Alzheimer's Research & Therapy 2019 11:79Discordant amyloid-β PET and CSF biomarkers and its clinical consequences
In vivo, high cerebral amyloid-β load has been associated with (i) reduced concentrations of Aβ42 in cerebrospinal fluid and (ii) increased retention using amyloid-β positron emission tomography. Although these t...Alzheimer's Research & Therapy 2019 11:78ABIDE Delphi study: topics to discuss in diagnostic consultations in memory clinics
Information given to patients and caregivers during the clinician-patient encounter varies considerably between memory clinic professionals. Patients and caregivers express a clear desire for more information....Alzheimer's Research & Therapy 2019 11:77The “rights” of precision drug development for Alzheimer’s disease
There is a high rate of failure in Alzheimer’s disease (AD) drug development with 99% of trials showing no drug-placebo difference. This low rate of success delays new treatments for patients and discourages i...Alzheimer's Research & Therapy 2019 11:76Enhancement of tripartite synapses as a potential therapeutic strategy for Alzheimer’s disease: a preclinical study in rTg4510 mice
The lack of effective treatment options for Alzheimer’s disease (AD) is of momentous societal concern. Synaptic loss is the hallmark of AD that correlates best with impaired memory and occurs early in the dise...Alzheimer's Research & Therapy 2019 11:75Use of mild cognitive impairment and prodromal AD/MCI due to AD in clinical care: a European survey
The diagnosis of mild cognitive impairment (MCI) refers to cognitive impairment not meeting dementia criteria. A survey among members of the American Association of Neurology (AAN) showed that MCI was consider...Alzheimer's Research & Therapy 2019 11:74Souvenaid in the management of mild cognitive impairment: an expert consensus opinion
Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis ...Alzheimer's Research & Therapy 2019 11:73Prediction of amyloid pathology in cognitively unimpaired individuals using voxel-wise analysis of longitudinal structural brain MRI
Magnetic resonance imaging (MRI) has unveiled specific alterations at different stages of Alzheimer’s disease (AD) pathophysiologic continuum constituting what has been established as “AD signature”. To what e...Alzheimer's Research & Therapy 2019 11:72A single-nuclei RNA sequencing study of Mendelian and sporadic AD in the human brain
Alzheimer’s disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heter...Alzheimer's Research & Therapy 2019 11:71Depression, subjective cognitive decline, and the risk of neurocognitive disorders
Depression and subjective cognitive decline (SCD) both predict neurocognitive disorders (NCD). However, the two correlate strongly with each other. It remains uncertain whether they reflect independent neurobi...Alzheimer's Research & Therapy 2019 11:70Music and emotion in Alzheimer’s disease
Alzheimer’s disease may compromise several musical competences, though no clear data is available in the scientific literature. Furthermore, music is capable of communicating basic emotions, but little is know...Alzheimer's Research & Therapy 2019 11:69Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer’s disease
Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assis...Alzheimer's Research & Therapy 2019 11:68Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer’s disease tau
Augmenting the brain clearance of toxic oligomers with small molecule modulators constitutes a promising therapeutic concept against tau deposition. However, there has been no test of this concept in animal mo...Alzheimer's Research & Therapy 2019 11:67Which features of subjective cognitive decline are related to amyloid pathology? Findings from the DELCODE study
Subjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer’s disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with in...Alzheimer's Research & Therapy 2019 11:66Tau and atrophy: domain-specific relationships with cognition
Late-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains r...Alzheimer's Research & Therapy 2019 11:65Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set
Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer’s disease, particularly in the early disease sta...Alzheimer's Research & Therapy 2019 11:64Towards a unified protocol for handling of CSF before β-amyloid measurements
Widespread implementation of Alzheimer’s disease biomarkers in routine clinical practice requires the establishment of standard operating procedures for pre-analytical handling of cerebrospinal fluid (CSF).Alzheimer's Research & Therapy 2019 11:63Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer’s disease
Retinal thickness can be measured non-invasively with optical coherence tomography (OCT) and may offer compelling potential as a biomarker for Alzheimer’s disease (AD). Retinal thinning is hypothesized to be a...Alzheimer's Research & Therapy 2019 11:62Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time
Subjective cognitive decline (SCD) defines a heterogeneous population, part of which having Alzheimer’s disease (AD). We aimed at characterizing SCD populations according to whether or not they referred to a m...Alzheimer's Research & Therapy 2019 11:61Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer’s disease spectrum
Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of th...Alzheimer's Research & Therapy 2019 11:60An experimental model of Braak’s pretangle proposal for the origin of Alzheimer’s disease: the role of locus coeruleus in early symptom development
The earliest brain pathology related to Alzheimer’s disease (AD) is hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons. Braak characterizes five pretangle tau stages preceding AD...Alzheimer's Research & Therapy 2019 11:59
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