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, molecular mechanisms, signaling pathways and biomarker signatures either individually or through complex gene-gene interactions, lifestyle and the environment. DISCUSSION:Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD. Another study has provided intriguing evidence that a low-frequency variant (rs63750847) in the APP gene is associated with a reduced risk of developing AD and a lower likelihood of age-related cognitive decline in elderly subjects without AD. SUMMARY:Recent years have witnessed tremendous development in genetics technology that has allowed full individualized genome-wide or genomic screening embracing all of the risk and protective variants for sAD, both across populations and within individuals. Hopefully, the integration of neurogenetics with systems biology and high-throughput genotyping will further pave the way to decipher all of the related causes, mechanisms, and biomarkers across the spectrum of distinct AD forms. After an almost lost apprentice decade in AD therapy development, the epoch of individualized asymptomatic screening and progress in primary and secondary prevention of sAD is probably at its dawn. Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Hampel H,Lista Sdoi
10.1186/alzrt165subject
Has Abstractpub_date
2013-03-18 00:00:00pages
11issue
2issn
1758-9193pii
alzrt165journal_volume
5pub_type
杂志文章abstract:BACKGROUND:Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stim...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00692-5
更新日期:2020-11-07 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
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更新日期:2019-12-05 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0336-4
更新日期:2018-01-29 00:00:00
abstract:BACKGROUND:Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0402-y
更新日期:2018-07-31 00:00:00
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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
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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:INTRODUCTION:The diagnosis of mild cognitive impairment (MCI) refers to cognitive impairment not meeting dementia criteria. A survey among members of the American Association of Neurology (AAN) showed that MCI was considered a useful diagnosis. Recently, research criteria have been proposed for the diagnosis of Alzheim...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0525-9
更新日期:2019-08-22 00:00:00
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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
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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
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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:Disclosure of amyloid positron emission tomography (PET) results to individuals without dementia has become standard practice in secondary prevention trials and also increasingly occurs in clinical practice. However, this is controversial given the current lack of understanding of the predictive value of a P...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0398-3
更新日期:2018-07-28 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:BACKGROUND:Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer's disease (AD) on both the systemic and central nervous system level. To study the extent and significance of these alterations in AD, quanti...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0551-7
更新日期:2019-11-28 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0143-0
更新日期:2015-09-15 00:00:00
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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
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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:BACKGROUND:Amyloid pathology, which is one of the characteristics of Alzheimer's disease (AD), results from altered metabolism of the beta-amyloid (Aβ) peptide in terms of synthesis, clearance, or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1-42 is evident in AD, and the CSF ratio Aβ42/Aβ40 has recentl...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00696-1
更新日期:2020-10-02 00:00:00
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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
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pub_type: 杂志文章
doi:10.1186/s13195-018-0401-z
更新日期:2018-09-11 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0326-y
更新日期:2017-12-16 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/alzrt29
更新日期:2010-04-12 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0450-3
更新日期:2019-01-22 00:00:00
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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
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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
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journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt260
更新日期:2014-05-29 00:00:00
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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
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journal_title:Alzheimer's research & therapy
pub_type: 已发布勘误
doi:10.1186/s13195-019-0493-0
更新日期:2019-05-07 00:00:00
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journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章
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更新日期:2016-03-07 00:00:00
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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