Abstract：
:Plaques found in the brains of patients suffering from Alzheimer's disease (AD) mainly consist of beta-amyloid (Abeta), which is produced by sequential cleaving of amyloid precursor protein (APP) by two proteolytic enzymes, beta- and gamma-secretases. Any change in the fine balance between these enzymes and their substrate may contribute to the etio-pathogenesis of AD. Indeed, the protein level and enzymatic activity of beta-secretase (BACE), but not its mRNA level, were found elevated in brain areas of AD patients who suffer a high load of Abeta plaque formation. Similarly, increased BACE activity but no mRNA change was observed in a transgenic mouse model of AD, tg2576, in which over expression of the Swedish mutated human APP leads to Abeta plaque formation and learning deficits. Based on the recent demonstration of four BACE splice variants with different enzymatic activity, the discrepancy between BACE activity and mRNA expression may be explained by the altered BACE alternative splicing. To test this hypothesis, we studied the expression of all BACE splice variants in different brain areas of tg2576 mice at age of 4 months and 1 year old. We found developmental and regional differences between wild-type and tg2576 mice. Our results indicate that over expression of APP in tg2576 mice leads to the altered alternative splicing of BACE and the increase of its enzymatically more active splice variant (I-501).
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Zohar O,Pick CG,Cavallaro S,Chapman J,Katzav A,Milman A,Alkon DLdoi
10.1016/j.neurobiolaging.2004.10.005subject
Has Abstractpub_date
2005-08-01 00:00:00pages
1167-75issue
8eissn
0197-4580issn
1558-1497pii
S0197-4580(04)00339-2journal_volume
26pub_type
杂志文章abstract：:The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the oth...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：1996-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90087-z
更新日期：1991-09-01 00:00:00
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journal_title：Neurobiology of aging
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更新日期：2013-01-01 00:00:00
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journal_title：Neurobiology of aging
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更新日期：2008-02-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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abstract：:Four biopsies of the brain cortex of patients with Alzheimer's disease were used for ultrastructural studies. Three-dimensional reconstruction and morphometric studies of three classical plaques were carried out to determine the distribution of the astrocytes and their processes, and spatial relationships between astr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90091-w
更新日期：1991-09-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.08.022
更新日期：2015-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.02.017
更新日期：2009-12-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2010-06-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.10.006
更新日期：2010-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00007-9
更新日期：1997-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2017.03.001
更新日期：2017-08-01 00:00:00
abstract：:Several independent linkage studies have mapped a broad susceptibility region for Alzheimer's disease (AD) on the long arm of chromosome 10. There are several biological candidate genes in this region, including choline acetyltransferase (CHAT). A number of studies have examined the role of CHAT genetic variants with ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.08.024
更新日期：2006-10-01 00:00:00
abstract：:Amyloid beta (Aβ) deposition and cognitive decline are key features of Alzheimer's disease. The relationship between Aβ status and changes in neuronal function over time, however, remains unclear. We evaluated the effect of baseline Aβ status on reference region spontaneous brain activity (SBA-rr) using resting-state ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.10.002
更新日期：2019-02-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90017-r
更新日期：1992-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.08.008
更新日期：2015-01-01 00:00:00
abstract：:To identify genes associated with frontotemporal dementia (FTD) in South-East Asia, targeted exome sequencing and C9orf72 genotyping was performed in 198 subjects (52 patients with FTD and 146 healthy controls) who were screened for mutations in 12 FTD-associated genes. We detected a homozygous TREM2 R47C mutation in ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.04.003
更新日期：2018-08-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90134-6
更新日期：1989-09-01 00:00:00
abstract：:The activity of beta-secretase (BACE1), the endo-protease essential for the production of amyloid beta (Abeta) peptides, is increased in brain of late-onset sporadic Alzheimer's disease (AD), and oxidative stress is the potential cause of this event. Oxidative stress up-regulates the expression and the activity of BAC...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.12.015
更新日期：2009-10-01 00:00:00
abstract：:The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer's disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.11.008
更新日期：2008-04-01 00:00:00
abstract：:The H1 MAPT haplotype in the 17q21 chromosomal region has been associated with several neurodegenerative diseases. Some reports have suggested that there is an association between genetic variants within the H1 haplotype with Parkinson's disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.09.011
更新日期：2011-03-01 00:00:00
abstract：:Age-related macular degeneration (AMD) has been linked to memory deficits, with no established neural mechanisms. We collected resting-state brain functional magnetic resonance imaging and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2020-11-01 00:00:00
abstract：:Cross-sectional studies have found declines in most measures of oculomotor function in older subjects compared to young controls, but no prior study has followed the same subjects over time. We measured saccade peak velocity, saccade delay time, smooth pursuit, optokinetic nystagmus (OKN), visual-vestibular-ocular-ref...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.07.009
更新日期：2006-09-01 00:00:00
abstract：:The effect of normal aging on the volume of the hippocampus and temporal cortex was assessed cross-sectionally with quantitative Magnetic Resonance Imaging (MRI) in 72 healthy men, spanning 5 decades of the adult age range (21 to 70 years). Neither the hippocampal nor cortical white matter volumes were significantly c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)00074-o
更新日期：1995-07-01 00:00:00
abstract：:Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and als...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2017-05-01 00:00:00
abstract：:Insertion and deletion variants (indels) within poly glycine tracts of fused in sarcoma (FUS) were initially reported as causative of disease in amyotrophic lateral sclerosis (ALS). Subsequent studies identified similar indels in controls and suggested that these indels may confer susceptibility to ALS. We aimed to el...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.09.029
更新日期：2012-02-01 00:00:00
abstract：:Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In thi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.06.019
更新日期：2020-11-01 00:00:00
abstract：:Synaptic failure underlies cognitive impairment in Alzheimer's disease (AD). Cumulative evidence suggests a strong link between mitochondrial dysfunction and synaptic deficits in AD. We previously found that oligomycin-sensitivity-conferring protein (OSCP) dysfunction produces pronounced neuronal mitochondrial defects...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2020-10-16 00:00:00
