Multidimensional plasma protein separation technique for identification of potential Alzheimer’s disease plasma biomarkers: a pilot study

2012 ◽  
Vol 119 (7) ◽  
pp. 779-788 ◽  
Author(s):  
Andreas Wolfram Henkel ◽  
Katharina Müller ◽  
Piotr Lewczuk ◽  
Thorsten Müller ◽  
Katrin Marcus ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Plasma Protein ◽  
Protein Separation ◽  
Separation Technique ◽  
Plasma Biomarkers

Different Morphology of Neuritic Plaques in the Archicortex of Alzheimer’s Disease with Comorbid Synucleinopathy: A Pilot Study

2020 ◽  
Vol 17 ◽  
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Jaromir Kukal ◽  
Radoslav Matej
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Time Course ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Dystrophic Neurites ◽  
Neuritic Plaques ◽  
Structural Differences ◽  
Lewy Body Variant

Background: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer’s disease (AD) and patients with AD in comorbidity with synucleinopathies. Methods: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer’s disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. Results: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. Conclusion: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

O3-02-05: Proteomic identification of plasma biomarkers for hippocampal atrophy in Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T161-T161
Author(s):  
Madhav Thambisetty ◽  
Andrew Simmons ◽  
Abdul Hye ◽  
Darragh O'Brien ◽  
James Campbell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Atrophy ◽  
Plasma Biomarkers ◽  
Proteomic Identification

Evaluation of the efficacy of animal-assisted therapy based on the reality orientation therapy protocol in Alzheimer's disease patients: a pilot study

2015 ◽  
Vol 16 (4) ◽  
pp. 240-246 ◽  
Author(s):  
Lucia Francesca Menna ◽  
Antonio Santaniello ◽  
Federica Gerardi ◽  
Annamaria Di Maggio ◽  
Graziella Milan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Animal Assisted Therapy ◽  
Reality Orientation ◽  
Therapy Protocol

Anticipatory and Reactive Grip Force Control in Patients with Alzheimer’s Disease: A Pilot Study

2021 ◽  
pp. 1-15
Author(s):  
Anna Gabriel ◽  
Carolin T. Lehner ◽  
Chiara Höhler ◽  
Thomas Schneider ◽  
Tessa P.T. Pfeiffer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Force Control ◽  
Grip Force ◽  
Object Manipulation ◽  
Step Test ◽  
Grip Force Control ◽  
Potential Biomarker ◽  
Neurological Conditions

Background: Alzheimer’s disease (AD) affects several cognitive functions and causes altered motor function. Fine motor deficits during object manipulation are evident in other neurological conditions, but have not been assessed in dementia patients yet. Objective: Investigate reactive and anticipatory grip force control in response to unexpected and expected load force perturbation in AD. Methods: Reactive and anticipatory grip force was investigated using a grip-device with force sensors. In this pilot study, fifteen AD patients and fourteen healthy controls performed a catching task. They held the device with one hand while a sandbag was dropped into an attached receptacle either by the experimenter or by the participant. Results: In contrast to studies of other neurological conditions, the majority of AD patients exerted lower static grip force levels than controls. Interestingly, patients who were slow in the Luria’s three-step test produced normal grip forces. The timing and magnitude of reactive grip force control were largely preserved in patients. In contrast, timing and extent of anticipatory grip forces were impaired in patients, although anticipatory control was generally preserved. These deficits were correlated with decreasing Mini-Mental State Examination scores. Apraxia scores, assessed by pantomime of tool-use, did not correlate with performance in the catching task. Conclusion: We interpreted the decreased grip force in AD in the context of loss of strength and lethargy, typical for patients with AD. The lower static grip force during object manipulation may emerge as a potential biomarker for early stages of AD, but more studies with larger sample sizes are necessary.

Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease

2018 ◽  
Vol 15 (10) ◽  
pp. 938-950 ◽  
Author(s):  
Martina Zverova ◽  
Eva Kitzlerova ◽  
Zdenek Fisar ◽  
Roman Jirak ◽  
Jana Hroudova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Apoe Genotype ◽  
Plasma Biomarkers ◽  
Plasma Melatonin ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Severity Of Dementia

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.

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