Abstract:
:Alzheimer's disease (AD) is the most common cause of dementia and a major contributor to disability and dependency among older people. AD pathogenesis is associated with the accumulation of amyloid-beta protein (Aβ) and/or hyperphosphorylated tau protein in the brain. At present, current therapies provide temporary symptomatic benefit, but do not treat the underlying disease. Recent research has thus focused on investigating the molecular and cellular pathways and processes involved in AD pathogenesis to support the development of effective disease-modifying agents. In accordance with the existing Aβ-cascade hypothesis for AD pathogenesis, immunotherapy has been the most extensively studied approach in Aβ-targeted therapy. Both passive and active immunotherapies have been shown to effectively reduce Aβ accumulation and prevent downstream pathology in preclinical models. Following AN1792, second-generation active immunotherapies have shown promising results in terms of antibody response and safety. Comparatively, tau immunotherapy is not as advanced, but preclinical data support its development into clinical trials. Results from active amyloid-based immunotherapy studies in preclinical models indicate that intervention appears to be more effective in early stages of amyloid accumulation, highlighting the importance of diagnosing AD as early as possible and undertaking clinical trials at this stage. This strategy, combined with improving our understanding of the complex AD pathogenesis, is imperative to the successful development of these disease-modifying agents. This paper will review the active immunotherapies currently in development, including the benefits and challenges associated with this approach.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Winblad B,Graf A,Riviere ME,Andreasen N,Ryan JMdoi
10.1186/alzrt237subject
Has Abstractpub_date
2014-01-30 00:00:00pages
7issue
1issn
1758-9193pii
alzrt237journal_volume
6pub_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::Recent trials of statins produced no benefit for subjects with Alzheimer's disease. These negative studies add to a growing list of negative clinical trials. These data point to a need for reevaluating the pathophysiology of late-onset Alzheimer's disease. Late-onset Alzheimer's disease might result from the cumulativ...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/alzrt101
更新日期:2012-01-16 00:00:00
abstract:INTRODUCTION:Weight loss has been described in 20% to 45% of patients with Alzheimer's disease (AD) and has been associated with adverse outcomes. Various mechanisms for weight loss in AD patients have been proposed, though none has been proven. This study aimed to elucidate a mechanism of weight loss in AD patients by...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0098-1
更新日期:2015-04-06 00:00:00
abstract:BACKGROUND:Association between kidney dysfunction and dementia has been studied in western cohorts, but with inconsistent conclusions which may be due to the different measurements of kidney function. We aim to verify the hypothesis that lower levels of kidney function would be associated with increased risk of inciden...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00729-9
更新日期:2021-01-11 00:00:00
abstract:INTRODUCTION:Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differ...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13195-015-0136-z
更新日期:2015-07-29 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:BACKGROUND:Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer's disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life cour...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00740-0
更新日期:2021-01-04 00:00:00
abstract:INTRODUCTION:Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies betwe...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-014-0090-1
更新日期:2015-02-11 00:00:00
abstract:BACKGROUND:Intracerebral inoculation of extracts from post-mortem human Alzheimer's disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cyt...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0513-0
更新日期:2019-06-29 00:00:00
abstract::The strongest known risk factors for late-onset Alzheimer disease (LOAD) remain a positive family history and the APOE epsilon4 allele. van Exel and colleagues used these known risk factors to identify high- and low-risk samples of middle-aged persons in whom they compared levels of inflammatory and vascular risk fact...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/alzrt29
更新日期:2010-04-12 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::The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-019-0485-0
更新日期:2019-04-22 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: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: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: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::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:Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target ei...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0401-z
更新日期:2018-09-11 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::The Alzheimer's Drug Discovery Foundation's 13th International Conference on Alzheimer's Drug Discovery was held on 10-11 September 2012 in Jersey City, NJ, USA. This meeting report provides an overview of Alzheimer's Drug Discovery Foundation-funded programs, ranging from novel biomarkers to accelerate clinical devel...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt159
更新日期:2013-02-04 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:Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer's disease by 2025. CASE PRESENTATION:Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer's researchers are confronting a clinical trial recruitment cris...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/s13195-018-0425-4
更新日期:2018-09-27 00:00:00
abstract:BACKGROUND:With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the lit...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0345-3
更新日期:2018-04-25 00:00:00
abstract:BACKGROUND:Blood-based biomarkers for Alzheimer's disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Bl...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00750-y
更新日期:2021-01-08 00:00:00
abstract:BACKGROUND:Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer's disease [AD] (preclinical or prodromal AD), mild cognitive impairment (MCI) and dementia is essential for economic evaluations of related health interventions. AIMS:To provide an overview of wh...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-020-00723-1
更新日期:2020-11-18 00:00:00
abstract:BACKGROUND:Cerebrovascular pathology, quantified by white matter lesions (WML), is known to affect cognition in aging, and is associated with an increased risk of dementia. The present study aimed to investigate whether higher functional connectivity in cognitive control networks mitigates the detrimental effect of WML...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0434-3
更新日期:2018-10-27 00:00:00
abstract:BACKGROUND: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-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in A...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0552-6
更新日期:2019-12-12 00:00:00
abstract:INTRODUCTION:Alzheimer's disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD. METHODS:We examined Clinical...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt269
更新日期:2014-07-03 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 Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (gene...
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/s13195-019-0506-z
更新日期:2019-06-04 00:00:00