Abstract:
:Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer's disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the "calpain-cathepsin hypothesis" of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Penke B,Paragi G,Gera J,Berkecz R,Kovács Z,Crul T,VÍgh Ldoi
10.2174/1567205015666180911151716subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1191-1212issue
13eissn
1567-2050issn
1875-5828pii
CAR-EPUB-92977journal_volume
15pub_type
杂志文章,评审abstract::Serum levels of β-amyloid (Aβ) peptides may represent an early biomarker in the diagnosis of Alzheimer's disease (AD). In the present study, we investigated the temporal kinetic changes in the levels of serum Aβ 1-42 and 40 in an amyloid precursor protein (APP)/presenilin (PS)1 double transgenic mouse model of AD. Ser...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/15672050113106660159
更新日期:2013-11-01 00:00:00
abstract::The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effe...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140505094808
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:To carry out meaningful comparisons on results of different research studies on mild cognitive impairment (MCI), it is critical to select an appropriate objective memory test to examine memory deficit. We aim to refine the operational criteria of amnestic MCI (aMCI) on neuropsychological tests that optimally ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150530202729
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Curcumin has been of interest in the field of Alzheimer's disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190816130516
更新日期:2019-01-01 00:00:00
abstract::In the last decade, several radiolabeled compounds have been developed for the imaging in vivo of amyloid pathology by means of Positron Emission Tomography (PET). Among these, 18F Florbetaben appear to be one of the most reliable for its high affinity for amyloid plaques in brain and its radio-chemical properties tha...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160620114309
更新日期:2017-01-01 00:00:00
abstract::Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing β-amyloid. Recent results of amyloid immunotherapy raised the question whether β-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hall...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510793611600
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. METHODS AND FINDINGS:AD patients aged 50-85 years were ra...
journal_title:Current Alzheimer research
pub_type: 杂志文章,随机对照试验
doi:10.2174/156720509787313961
更新日期:2009-02-01 00:00:00
abstract::Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer's dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on p...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666160314151247
更新日期:2016-01-01 00:00:00
abstract::Apoptosis has been postulated to play a possible causal role in the onset of Alzheimer's disease due to shortage of trophic supply, deafferentation and excessive production of free radicals. Many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis. In view of ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506778249416
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disease characterised by a progressive decline in cognitive function and represents a major healthcare challenge worldwide. Increasing evidence indicates that mitochondrial dysfunction mediated oxidative stress plays a significant role in the pathophysiological...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205014666170203095802
更新日期:2018-01-01 00:00:00
abstract::Mild cognitive impairment (MCI) is a nosological entity associated with a higher risk of developing dementia. Previous evidence indicates that behavioral and psychological symptoms of dementia (BPSDs) frequently occur in individuals of MCI. These neuropsychiatric manifestations may predict conversion to dementia. Howe...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160502123129
更新日期:2016-01-01 00:00:00
abstract::Amyloid-β protein (Aβ) accumulates in the neurons of Alzheimer's disease (AD) patients at an early stage of the disease. Recently, we found that Aβ with a toxic turn at positions 22 and 23 accumulates in neurons in AD brain. Here, we studied the accumulation of Aβ, toxic turn Aβ and high-molecular-weight Aβ oligomers ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510793499075
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:Accumulating evidence suggests that multi-target directed ligands have great potential for the treatment of complex diseases such as Alzheimer's Disease (AD). OBJECTIVE:To evaluate novel chimeric 8-hydroxyquinoline ligands with merged pharmacophores as potential multifunctional ligands for AD. METHODS:Nitr...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666191010130351
更新日期:2019-01-01 00:00:00
abstract::This article presents a new paradigm of Artificial Neural Networks (ANNs): the Auto-Contractive Maps (Auto-CM). The Auto-CM differ from the traditional ANNs under many viewpoints: the Auto-CM start their learning task without a random initialization of their weights, they meet their convergence criterion when all thei...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720508785908928
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reduci...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180404160625
更新日期:2018-01-01 00:00:00
abstract::The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795255982
更新日期:2011-03-01 00:00:00
abstract::Soluble amyloid beta (Abeta) oligomers might trigger early cognitive impairment in Alzheimer's Disease (AD) through the impairment of proper neuronal network function. We have recently shown that the short sequence Abeta(25-35) affects the spontaneous activity in hippocampal slices, when was added to the bath, at high...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720510791383859
更新日期:2010-08-01 00:00:00
abstract::Rigorous scientific research has identified multiple interactive mechanisms that parallel and are likely causative of the development of Alzheimer's disease (AD). Causative mechanisms include genomics, the creation of amyloid beta (Abeta), factors inhibiting the Abeta removal process, the transformation of Abeta to it...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506776383068
更新日期:2006-04-01 00:00:00
abstract::Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720501301151207100616
更新日期:2016-01-01 00:00:00
abstract::Anesthesia and surgery have been reported to produce long-term cognitive problems, and to accelerate neurodegenerative disorders in the elderly. In previous work, we found that inhaled anesthetics enhance fibril formation and cytotoxicity of amyloid beta peptide. In this work we show that the inhaled anesthetics halot...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720507781077278
更新日期:2007-07-01 00:00:00
abstract::Gamma-secretase is a multi-protein complex that proteolyzes the transmembrane region of the amyloid beta-peptide (Abeta) precursor (APP), producing the Abeta peptide implicated in the pathogenesis of Alzheimer's disease (AD). This protease has been a top target for AD, and various inhibitors have been identified, incl...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720508783954767
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal-directed to the development of new anticholinesterase agents with the expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule with two or more ph...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180711110750
更新日期:2018-01-01 00:00:00
abstract::Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD). The main endogenous antioxidant, glutathione (GSH), has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH level...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150302160308
更新日期:2015-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720501209151019105647
更新日期:2015-01-01 00:00:00
abstract::The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropatholo...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720510790691218
更新日期:2010-03-01 00:00:00
abstract::Memory loss is a prominent health concern, second only to heart disease for older individuals. Docosahexaenoic acid (DHA), the principle omega-3 fatty acid in brain and heart, plays an important role in neural and cardiac function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Al...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510791050911
更新日期:2010-05-01 00:00:00
abstract::Alzheimer's disease (AD) is currently the most prominent form of dementia among the elderly. Although AD manifests in late adult life, it is not clear when the disease actually starts and how long the neuropathological processes take to develop AD. The major unresolved question is the timing and the nature of triggeri...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362164
更新日期:2007-04-01 00:00:00
abstract::CATIE-AD was a multicenter effectiveness trial of atypical antipsychotics in patients with agitation and psychosis associated with AD who resided in the community. The study enrolled 421 participants. In this paper we present and discuss baseline characteristics of participants (demographics, cognitive, behavioral, an...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/156720507781077214
更新日期:2007-07-01 00:00:00
abstract::Recent studies have shown that the translocase of outer mitochondrial membrane 40 homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which is associated with an increase in AD incidence among APOE 3 carriers. Current methods to isotype the poly-T region rely on long PCR, subcloning and sequenc...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512804142921
更新日期:2012-12-01 00:00:00