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 silico studies of amyloid β-protein oligomers, and discuss important caveats that should be considered in the evaluation of these results. This article is divided into four sections that mirror the main approaches used in the field to better understand oligomers: (1) attempts to locate and examine oligomers in vivo in situ; that is, without removing these species from their environment; (2) studies involving oligomers extracted from human or animal tissues and the subsequent characterization of their properties ex vivo; (3) studies of oligomers that have been produced synthetically and studied using a reductionist approach in relatively simple in vitro biophysical systems; and (4) computational studies of oligomers in silico. These multiple orthogonal approaches have revealed much about the molecular and cell biology of amyloid β-protein. However, as informative as these approaches have been, the amyloid β-protein oligomer system remains enigmatic.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Hayden EY,Teplow DBdoi
10.1186/alzrt226subject
Has Abstractpub_date
2013-11-29 00:00:00pages
60issue
6issn
1758-9193pii
alzrt226journal_volume
5pub_type
杂志文章,评审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. METHOD...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/alzrt186
更新日期：2013-06-13 00:00:00
abstract：BACKGROUND:Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid β (Aβ) protofibrils. METHODS:Here we describe the first clinical study with BAN2401. Safety and tolerability were...
journal_title：Alzheimer's research & therapy
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1186/s13195-016-0181-2
更新日期：2016-04-06 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: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:Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer's disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone vari...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-020-00745-9
更新日期：2021-01-20 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：:Therapeutic products that depend on the use of an in vitro diagnostic biomarker test to confirm their effectiveness are increasingly being developed. Use of biomarkers is particularly meaningful in the context of selecting the patient population where the therapeutic treatment is believed to be efficacious (patient en...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章,评审
doi：10.1186/alzrt142
更新日期：2012-10-17 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:The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS:Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-017-0280-8
更新日期：2017-07-27 00:00:00
abstract：BACKGROUND:The application of advanced sequencing technologies and improved mass-spectrometry platforms revealed significant changes in gene expression and lipids in Alzheimer's disease (AD) brain. The results so far have prompted further research using "multi-omics" approaches. These approaches become particularly rel...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-019-0558-0
更新日期：2019-12-30 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
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：BACKGROUND: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 trial design, and geographical regions. METHODS:Placebo-controlled randomized AD clinical trials were ...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-020-00630-5
更新日期：2020-05-26 00:00:00
abstract：BACKGROUND:The retina and brain share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in Alzheimer's disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA). METHODS:In this cross-sectional study, 24 AD participants, 37 MCI part...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-020-00724-0
更新日期：2020-12-04 00:00:00
abstract：:Parkinson's disease, the most common movement disorder, results in an insidious reduction for patients in quality of life and ability to function. A hallmark of Parkinson's disease is the brain accumulation of neuronal cytoplasmic inclusions comprised of the protein α-synuclein. The presence of α-synuclein brain aggre...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章,评审
doi：10.1186/alzrt151
更新日期：2012-12-17 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：:Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting older people worldwide. It is a progressive disorder mainly characterized by the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles within the brain parenchyma. It is now well accepted that neuroinflammation constitutes an ...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-015-0125-2
更新日期：2015-04-15 00:00:00
abstract：BACKGROUND:The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the fiel...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-017-0265-7
更新日期：2017-06-06 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：INTRODUCTION:Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic cause of familial frontotemporal deme...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/alzrt136
更新日期：2012-08-16 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：:Dementia with Lewy bodies (DLB) has become the second most common neurodegenerative dementia due to demographic ageing. Differential diagnosis is still troublesome especially in early stages of the disease, since there is a great clinical and neuropathological overlap primarily with Alzheimer's disease and Parkinson's...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章,评审
doi：10.1186/s13195-014-0072-3
更新日期：2014-10-16 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：BACKGROUND:Alzheimer's disease (AD) pathophysiology is mostly (>95%) not inherited in a Mendelian fashion. Such sporadic AD (sAD) forms do not exhibit familial aggregation and are characterized by complex genetic inheritance. Growing evidence indicates that multiple genes contribute to sAD-characteristic endophenotypes...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/alzrt165
更新日期：2013-03-18 00:00:00
abstract：BACKGROUND:Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstruct...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-017-0329-8
更新日期：2018-01-09 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：BACKGROUND: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. METHODS:This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 p...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-020-00618-1
更新日期：2020-05-06 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:Recent Genome Wide Association Studies (GWAS) have identified novel rare coding variants in immune genes associated with late onset Alzheimer's disease (LOAD). Amongst these, a polymorphism in phospholipase C-gamma 2 (PLCG2) P522R has been reported to be protective against LOAD. PLC enzymes are key elements ...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-019-0469-0
更新日期：2019-02-02 00:00:00
abstract：BACKGROUND:Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and...
journal_title：Alzheimer's research & therapy
pub_type： 杂志文章
doi：10.1186/s13195-019-0477-0
更新日期：2019-03-21 00:00:00
