Abstract：
:In a prospective study of dementia in Flanders (Belgium), we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal genes linked to neurodegenerative brain diseases. In this group, the onset or inclusion age was 59.9 ± 8.2 years and 27.4% had a positive family history. We used a panel of 16 major genes linked to Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and prion diseases. In addition, we tested for the presence of a pathogenic C9orf72 repeat expansion. We identified 13 rare variants in 15 patients, including a carrier of variants in 2 different genes. Six patients (2.84%), carried a mutation in a Mendelian causal gene, that is, APP, MAPT, SOD1, TBK1, and C9orf72. In the other 7 patients, 7 variants were of uncertain significance, including a frameshift mutation in PSEN2, p.G359Lfs*74, in 2 patients sharing a common haplotype, and in LRRK2, p.L2063fs*. Expression studies showed reduced PSEN2 and a near complete loss of LRRK2, in lymphoblast cells or brain material of these patients. Overall, our study underscores the relevance of genetic testing of known causal genes in early-onset patients with symptomatology of neurodegenerative dementia but an unclear clinical diagnosis. A positive genetic result can help to obtain a precise diagnosis as well as a better understanding of the presence of multiple affected relatives in the family.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Perrone F,Cacace R,Van Mossevelde S,Van den Bossche T,De Deyn PP,Cras P,Engelborghs S,van der Zee J,Van Broeckhoven Cdoi
10.1016/j.neurobiolaging.2018.04.015subject
Has Abstractpub_date
2018-09-01 00:00:00pages
292.e7-292.e14eissn
0197-4580issn
1558-1497pii
S0197-4580(18)30149-0journal_volume
69pub_type
杂志文章abstract：:The total number of the neuromelanin-containing neurons of the nucleus coeruleus was determined by means of a newly developed unbiased stereological counting scheme and a low-cost apparative set-up. The individuals (n = 20, age from 49-98 years) included in this study were carefully examined for absence of neurologica...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00034-1
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abstract：:Based on evidence that high Mg2+ counteracts age-related declines in synaptic plasticity, and that aged rat hippocampal neurons exhibit prolonged Ca2+-dependent K+ currents, it is proposed that an underlying cause of altered Ca2+ homeostasis during brain aging may be an increased membrane conductance to Ca2+. An appar...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(87)90074-1
更新日期：1987-07-01 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
doi：10.1016/j.neurobiolaging.2020.07.020
更新日期：2020-11-01 00:00:00
abstract：:Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In c...
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
abstract：:Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the 2 most common causes of dementia. We compared the regional metabolism on 18F-fluorodeoxyglucose positron emission tomography (PET) among 21 control subjects and cognitively impaired patients due to DLB (N = 63) and AD (N = 38). All participants under...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.10.020
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.06.014
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.06.016
更新日期：2017-11-01 00:00:00
abstract：:Mutants of presenilin 1 (PS1) increase neuronal cell death causing autosomal-dominant familial Alzheimer's disease (FAD). Recent literature shows that treatment of neuronal cultures with low concentrations of trypsin, a member of the serine family of proteases, protects neurons from toxic insults by binding to the pro...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.028
更新日期：2016-06-01 00:00:00
abstract：:Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00081-5
更新日期：1998-09-01 00:00:00
abstract：:Variants in exon 4 of gene encoding GLT8D1 (glycosyltransferase 8 domain containing 1) gene have recently been suggested as a novel cause of amyotrophic lateral sclerosis (ALS). In addition, there is a synergism between GLT8D1 and ARPP21 (cAMP Regulated Phosphoprotein 21) variants for ALS. However, this observation ha...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.09.013
更新日期：2020-01-01 00:00:00
abstract：:Beta amyloid (Aβ) is well accepted to play a central role in the pathogenesis of Alzheimer's disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aβ-induced neurotoxicity in rat hippocampus. Aβ 1-42 was injected bilaterally to the hippocampus CA1 region of adult male...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.10.003
更新日期：2017-01-01 00:00:00
abstract：:An age-related phosphorylation of the 200kD neurofilament protein (NF200) has been observed in the axons of cerebellar basket cells of normal human fixed brain tissue from individuals older than 60 years, but not in younger individuals. The probe for this study was the monoclonal antibody SMI-34 which detects a phosph...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90059-6
更新日期：1989-05-01 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：:Demonstrations that grip strength has predictive power in relation to a range of health conditions-even when these are assessed decades later-has motivated claims that hand-grip dynamometry has the potential to serve as a "vital sign" for middle-aged and older adults. Central to this belief has been the assumption tha...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2018.07.023
更新日期：2018-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.011
更新日期：2015-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.011
更新日期：2006-03-01 00:00:00
abstract：:Evidence indicates that oxidative stress-induced damage to DNA, protein, and other cellular components contributes to the progression of Alzheimer's disease (AD). Several studies indicate that postmitotic neurons have a reduced capacity for some types of DNA repair, which is further compromised by aging. Thus in AD, t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.009
更新日期：2006-04-01 00:00:00
abstract：:Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)00062-0
更新日期：1996-07-01 00:00:00
abstract：:There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast admini...
journal_title：Neurobiology of aging
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.neurobiolaging.2019.01.014
更新日期：2019-05-01 00:00:00
abstract：:Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant pre...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.09.006
更新日期：2015-12-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.021
更新日期：2006-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90034-u
更新日期：1992-03-01 00:00:00
abstract：:Age-related changes in resting levels of the free intracellular calcium concentration ([Ca2+]i) as well as alterations of the rise in [Ca2+]i following depolarization have been investigated in acutely isolated brain cells of various regions of the rat brain. Characterization of the Ca2+ responses following KCl depolar...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)84400-9
更新日期：1996-07-01 00:00:00
abstract：:The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.04.007
更新日期：2010-03-01 00:00:00
abstract：:Frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17) are hereditary tauopathies affecting at least 50 known kindred worldwide. Most kindred present with severe behavioral or psychiatric manifestations progressing to dementia, while some kindred first manifest a parkinsonian-plus syndrome. Nine ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(00)00202-5
更新日期：2001-01-01 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
abstract：:A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.03.017
更新日期：2020-08-01 00:00:00
abstract：:In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and tota...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.10.019
更新日期：2015-02-01 00:00:00
abstract：:Increased life expectancy impacts directly on the number of older people worldwide with the associated increase in neurodegenerative diseases. Besides their social implications, the different forms of dementia, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies or frontotemporal dementia, sh...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2018.10.006
更新日期：2019-02-01 00:00:00
abstract：:Cerebral gray-matter volume (GMV) decreases in normal aging but the extent of the decrease may be experience-dependent. Bilingualism may be one protective factor and in this article we examine its potential protective effect on GMV in a region that shows strong age-related decreases-the left anterior temporal pole. Th...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.010
更新日期：2014-09-01 00:00:00
