Abstract:
INTRODUCTION:Peripheral biomarkers to diagnose Alzheimer's disease (AD) have not been established. Given parallels between neuron and platelet biology, we hypothesized platelet membrane-associated protein changes may differentiate patients clinically defined with probable AD from noncognitive impaired controls. METHODS:Purified platelets, confirmed by flow cytometry were obtained from individuals before fractionation by ultracentrifugation. Following a comparison of individual membrane fractions by SDS-PAGE for general proteome uniformity, equal protein weight from the membrane fractions for five representative samples from AD and five samples from controls were pooled. AD and control protein pools were further divided into molecular weight regions by one-dimensional SDS-PAGE, prior to digestion in gel. Tryptic peptides were analyzed by reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Ionized peptide intensities were averaged for each identified protein in the two pools, thereby measuring relative protein abundance between the two membrane protein pools. Log2-transformed ratio (AD/control) of protein abundances fit a normal distribution, thereby permitting determination of significantly changed protein abundances in the AD pool. RESULTS:We report a comparative analysis of the membrane-enriched platelet proteome between patients with mild to moderate AD and cognitively normal, healthy subjects. A total of 144 proteins were determined significantly altered in the platelet membrane proteome from patients with probable AD. In particular, secretory (alpha) granule proteins were dramatically reduced in AD. Of these, we confirmed significant reduction of thrombospondin-1 (THBS1) in the AD platelet membrane proteome by immunoblotting. There was a high protein-protein connectivity of proteins in other pathways implicated by proteomic changes to the proteins that define secretory granules. CONCLUSIONS:Depletion of secretory granule proteins is consistent with a preponderance of post-activated platelets in circulation in AD. Significantly changed pathways implicate additional AD-related defects in platelet glycoprotein synthesis, lipid homeostasis, amyloidogenic proteins, and regulators of protease activity, many of which may be useful plasma membrane-expressed markers for AD. This study highlights the utility of LC-MS/MS to quantify human platelet membrane proteins and suggests that platelets may serve as a source of blood-based biomarkers in neurodegenerative disease.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Donovan LE,Dammer EB,Duong DM,Hanfelt JJ,Levey AI,Seyfried NT,Lah JJdoi
10.1186/alzrt186subject
Has Abstractpub_date
2013-06-13 00:00:00pages
32issue
3issn
1758-9193pii
alzrt186journal_volume
5pub_type
杂志文章abstract:BACKGROUND:Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer's disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD. METHODS:After treatment ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0226-6
更新日期:2016-12-13 00:00:00
abstract::In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt199
更新日期:2013-07-08 00:00:00
abstract:INTRODUCTION:There have been recent reports about a decline in dementia incidence, but only little is known about trends in the mortality of patients with dementia. Only the simultaneous analysis of both trends can inform whether the reported decline in dementia has led to a compression of dementia into higher ages. M...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0146-x
更新日期:2015-11-05 00:00:00
abstract:BACKGROUND:Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0179-9
更新日期:2016-03-16 00:00:00
abstract:BACKGROUND:Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00602-9
更新日期:2020-03-31 00:00:00
abstract::Symptomatic treatments for Alzheimer's disease should retain a place in the advanced stages of disease since their actions on these symptoms, even if not modifying the course of disease, are critical for improving patients' comfort and reducing the burden felt by caregivers, especially those facing behavioral disorder...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt228
更新日期:2013-12-11 00:00:00
abstract:BACKGROUND:Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to f...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0377-8
更新日期:2018-05-24 00:00:00
abstract:BACKGROUND:Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimer's disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. METHODS:We produced a novel strain of transgenic mice that could be used t...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0202-1
更新日期:2016-09-05 00:00:00
abstract:BACKGROUND:The Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Ce...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0478-z
更新日期:2019-03-21 00:00:00
abstract:BACKGROUND:Amyloid-β 1-42 (Aβ1-42) peptide is a well-established cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD). Reduced levels of Aβ1-42 are indicative of AD, but significant variation in the absolute concentrations of this analyte has been described for both healthy and diseased populations. Preanal...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0445-0
更新日期:2018-11-28 00:00:00
abstract:BACKGROUND:The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between pa...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-016-0201-2
更新日期:2016-08-12 00:00:00
abstract:BACKGROUND:There is increasing evidence that dementia risk associated with vascular disorders is age dependent. Large population-based studies of incident dementia are necessary to further elucidate this effect. Therefore, the aim of the present study was to determine the association of vascular disorders with incident...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0496-x
更新日期:2019-05-17 00:00:00
abstract:BACKGROUND: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. Daily functional tasks are innately cognitive demanding and involve components found in common exercis...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13195-019-0548-2
更新日期:2019-12-04 00:00:00
abstract:BACKGROUND:In Alzheimer's disease, beta-amyloid peptides in the brain aggregate into toxic oligomers and plaques, a process which is associated with neuronal degeneration, memory loss, and cognitive decline. One therapeutic strategy is to decrease the production of potentially toxic beta-amyloid species by the use of i...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13195-016-0178-x
更新日期:2016-03-07 00:00:00
abstract:BACKGROUND:Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0353-3
更新日期:2018-02-26 00:00:00
abstract::The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed sinc...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-014-0068-z
更新日期:2014-09-24 00:00:00
abstract:BACKGROUND:Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-020-00588-4
更新日期:2020-03-02 00:00:00
abstract:INTRODUCTION:MAPT encodes for tau, the predominant component of neurofibrillary tangles that are neuropathological hallmarks of Alzheimer's disease (AD). Genetic association of MAPT variants with late-onset AD (LOAD) risk has been inconsistent, although insufficient power and incomplete assessment of MAPT haplotypes ma...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt268
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:The goal was to identify which neurochemicals differ in professional athletes with repetitive brain trauma (RBT) when compared to healthy controls using a relatively new technology, in vivo Localized COrrelated SpectroscopY (L-COSY). METHODS:To achieve this, L-COSY was used to examine five former professi...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0094-5
更新日期:2015-03-15 00:00:00
abstract:BACKGROUND:A growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brai...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-018-0347-1
更新日期:2018-02-20 00:00:00
abstract::Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-020-00703-5
更新日期:2020-10-29 00:00:00
abstract:BACKGROUND:Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0170-5
更新日期:2016-02-12 00:00:00
abstract:INTRODUCTION:Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, me...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt279
更新日期:2014-08-11 00:00:00
abstract:BACKGROUND:Errorless learning (EL) is a method for optimizing learning, which uses feed-forward instructions in order to prevent people from making mistakes during the learning process. The majority of previous studies on EL taught patients with dementia artificial tasks of little or no relevance for their daily lives....
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13195-017-0247-9
更新日期:2017-03-23 00:00:00
abstract:INTRODUCTION:There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD. MET...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt53
更新日期:2010-10-15 00:00:00
abstract:INTRODUCTION:The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial. METHODS:This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in t...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-014-0081-2
更新日期:2015-02-03 00:00:00
abstract:INTRODUCTION:The Third National Alzheimer Plan (2008-2012) was a major public health initiative in France that included €200 million of funding for research in Alzheimer disease and related disorders (AD). The aim of this study was to document trends in French academic output in AD following the implementation of the p...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0144-z
更新日期:2015-09-26 00:00:00
abstract:INTRODUCTION:Behavioural and psychological symptoms of dementia (BPS) include depressive symptoms, anxiety, apathy, sleep problems, irritability, psychosis, wandering, elation and agitation, and are common in the non-demented and demented population. METHODS:We have undertaken a systematic review of reviews to give a ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt131
更新日期:2012-07-11 00:00:00
abstract::The oligomer cascade hypothesis, which states that oligomers are the initiating pathologic agents in Alzheimer's disease, has all but supplanted the amyloid cascade hypothesis, which suggested that fibers were the key etiologic agents in Alzheimer's disease. We review here the results of in vivo, in vitro and in silic...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt226
更新日期:2013-11-29 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by neuropathologic changes involving beta-amyloid (Aβ), tau, neuronal loss, and other associated biological events. While levels of cerebrospinal fluid (CSF) Aβ and tau peptides have enhanced the antemortem detection of AD-specifi...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13195-018-0426-3
更新日期:2018-09-25 00:00:00