TY  - JOUR
AB  - Patients with amyotrophic lateral sclerosis (ALS) show substantial differences in disease progression and survival. However, the genetic contribution to the extremes of this spectrum remains poorly characterized. We unbiasedly selected and genotyped 102 ALS patients with very short (<15 months) and 90 with very long survival (>100 months) from the ALS registry of Ulm University using whole-exome sequencing and C9orf72 repeat expansion testing followed by a clinicogenetic correlation analysis. Clinically, groups significantly differed regarding site of disease onset, age at onset, BMI at diagnosis, disease progression rates, and diagnostic latency. We found a monogenic disease cause in 31 patients (16%) without significant differences in patients with short and long survival (19% vs. 13%; p = 0.41), but differences in the genotypic architecture. C9orf72 expansions and FUS mutations were only found in fast progressors, whereas SOD1 variants were frequent in both groups contributing 52% of all monogenic cases–33% among fast and 75% among slow variants. Our genotype-phenotype correlation may be relevant for genetic counseling, estimation of prognosis, and therapeutic decisions.
AU  - Witzel, S.*
AU  - Wagner, M.
AU  - Zhao, C.
AU  - Kandler, K.*
AU  - Graf, E.
AU  - Berutti, R.*
AU  - Oexle, K.
AU  - Brenner, D.*
AU  - Winkelmann, J.
AU  - Ludolph, A.C.*
C1  - 65852
C2  - 52942
SP  - 117-126
TI  - Fast versus slow disease progression in amyotrophic lateral sclerosis–clinical and genetic factors at the edges of the survival spectrum.
JO  - Neurobiol. Aging
VL  - 119
PY  - 2022
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Several studies reported amyotrophic lateral sclerosis (ALS)-linked mutations in TBK1, OPTN, VCP, UBQLN2, and SQSTM1 genes encoding proteins involved in autophagy. SQSTM1 was originally identified by a candidate gene approach because it encodes p62, a multifunctional protein involved in protein degradation both through proteasomal regulation and autophagy. Both p62 and optineurin (encoded by OPTN) are direct interaction partners and substrates of TBK1, and these 3 proteins form the core of a genetic and functional network that may connect autophagy with ALS. Considering the molecular and conceptual relevance of the TBK1/OPTN/SQSTM1 "triangle," we here performed a targeted screen for SQSTM1 variants in 486 patients with familial ALS from Germany and Sweden by analyzing whole-exome sequencing data. We report 9 novel and 5 previously reported rare variants in SQSTM1 and discuss the current evidence for SQSTM1 as a primary disease gene for ALS. We conclude that the evidence for causality remains vague for SQSTM1 and is weaker than for the other autophagy genes, for example, TBK1 and OPTN. (C) 2019 Elsevier Inc. All rights reserved.
AU  - Yilmaz, R.*
AU  - Müller, K.*
AU  - Brenner, D.*
AU  - Volk, A.E.*
AU  - Borck, G.*
AU  - Hermann, A.*
AU  - Meitinger, T.
AU  - Strom, T.M.
AU  - Danzer, K.M.*
AU  - Ludolph, A.C.*
AU  - Andersen, P.M.*
AU  - Weishaupt, J.H.*
C1  - 57709
C2  - 48003
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 139.e9-139.e15
TI  - SQSTM1/p62 variants in 486 patients with familial ALS from Germany and Sweden.
JO  - Neurobiol. Aging
VL  - 87
PB  - Elsevier Science Inc
PY  - 2020
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin and cortisol, that is, indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomnographically assessed and blood samples were repeatedly collected. Elderly compared with young participants displayed increased early-sleep cortisol concentrations (p < 0.04) and reductions in slow wave and REM sleep (p < 0.001). Insulin administration reduced cortisol levels between 2300 hours and 0020 hours in the elderly (p = 0.03) but not young participants (p = 0.56; p = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age.
AU  - Thienel, M.
AU  - Wilhelm, I.*
AU  - Benedict, C.*
AU  - Born, J.
AU  - Hallschmid, M.
C1  - 50908
C2  - 42996
CY  - New York
SP  - 170-174
TI  - Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans.
JO  - Neurobiol. Aging
VL  - 54
PB  - Elsevier Science Inc
PY  - 2017
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
AU  - Wang, L.*
AU  - Heckman, M.G.*
AU  - Aasly, J.O.*
AU  - Annesi, G.*
AU  - Bozi, M.*
AU  - Chung, S.J.*
AU  - Clarke, C.*
AU  - Crosiers, D.*
AU  - Eckstein, G.N.
AU  - Garraux, G.*
AU  - Hadjigeorgiou, G.M.*
AU  - Hattori, N.*
AU  - Jeon, B.*
AU  - Kim, Y.J.*
AU  - Kubo, M.*
AU  - Lesage, S.*
AU  - Lin, J.J.*
AU  - Lynch, T.*
AU  - Lichtner, P.
AU  - Mellick, G.D.*
AU  - Mok, V.*
AU  - Morrison, K.E.*
AU  - Quattrone, A.*
AU  - Satake, W.*
AU  - Silburn, P.A.*
AU  - Stefanis, L.*
AU  - Stockton, J.D.*
AU  - Tan, E.K.*
AU  - Toda, T.*
AU  - Brice, A.*
AU  - van Broeckhoven, C.*
AU  - Uitti, R.J.*
AU  - Wirdefeldt, K.*
AU  - Wszolek, Z.*
AU  - Xiromerisiou, G.*
AU  - Maraganore, D.M.*
AU  - Gasser, T.*
AU  - Kruger, R.*
AU  - Farrer, M.J.*
AU  - Ross, O.A.*
AU  - Sharma, M.*
C1  - 50154
C2  - 42296
CY  - New York
SP  - 217.e1-217.e4
TI  - Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: Analysis of a large multicenter study.
JO  - Neurobiol. Aging
VL  - 49
PB  - Elsevier Science Inc
PY  - 2017
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
AU  - Guerreiro, R.*
AU  - Escott-Price, V.*
AU  - Darwent, L.*
AU  - Parkkinen, L.*
AU  - Ansorge, O.*
AU  - Hernandez, D.G.*
AU  - Nalls, M.A.*
AU  - Clark, L.*
AU  - Honig, L.*
AU  - Marder, K.*
AU  - van der Flier, W.*
AU  - Holstege, H.*
AU  - Louwersheimer, E.*
AU  - Lemstra, A.*
AU  - Scheltens, P.*
AU  - Rogaeva, E.*
AU  - St. George-Hyslop, P.H.*
AU  - Londos, E.*
AU  - Zetterberg, H.*
AU  - Ortega-Cubero, S.*
AU  - Pastor, P.*
AU  - Ferman, T.J.*
AU  - Graff-Radford, N.R.*
AU  - Ross, O.A.*
AU  - Barber, I.*
AU  - Braae, A.*
AU  - Brown, K.*
AU  - Morgan, K.*
AU  - Maetzler, W.*
AU  - Berg, D.*
AU  - Troakes, C.*
AU  - Al-Sarraj, S.*
AU  - Lashley, T.*
AU  - Compta, Y.*
AU  - Revesz, T.*
AU  - Lees, A.*
AU  - Cairns, N.J.*
AU  - Halliday, G.M.*
AU  - Mann, D.*
AU  - Pickering-Brown, S.*
AU  - Powell, J.*
AU  - Lunnon, K.*
AU  - Lupton, M.K.*
AU  - International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T.
AU  - Lichtner, P.)
AU  - Dickson, D.W.*
AU  - Hardy, J.*
AU  - Singleton, A.*
AU  - Bras, J.*
C1  - 47859
C2  - 39605
SP  - 214.e7-214.e10
TI  - Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
JO  - Neurobiol. Aging
VL  - 38
PY  - 2016
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - A recent study in autopsy-confirmed Parkinson's disease (PD) patients and controls revived the debate about the role of PARK10 in this disorder. In an attempt to replicate these results and further understand the role of this locus in the risk and age at onset of PD, we decided to explore NeuroX genotyping and whole exome sequencing data from 2 large independent cohorts of clinical patients and controls from the International Parkinson's Disease Genomic Consortium. A series of single-variant and gene-based aggregation (sequence kernel association test and combined multivariate and collapsing test) statistical tests suggested that common and rare genetic variation in this locus do not influence the risk or age at onset of clinical PD.
AU  - Simon-Sanchez, J.*
AU  - Heutink, P.*
AU  - Gasser, T.*
AU  - International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T.
AU  - Lichtner, P.)
C1  - 46736
C2  - 37773
SP  - 2907.e13-2907.e17
TI  - Variation in PARK10 is not associated with risk and age at onset of Parkinson's disease in large clinical cohorts.
JO  - Neurobiol. Aging
VL  - 36
IS  - 10
PY  - 2015
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Growing evidence suggests that Parkinson's disease (PD) patients have a lower risk for most types of cancer except for melanoma, which has a modest positive association with PD. Pigmentation genes have been hypothesized to contribute to this association. We therefore examined whether genetic susceptibility loci for pigmentation or melanoma was associated with PD risk in 2 large independent datasets. In the Parkinson's Genes and Environment (PAGE) study, we examined 11 single-nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies (GWAS) of pigmentation or melanoma in relation to PD among 808 PD cases and 1623 controls; furthermore, we also examined the colors of hair, eye, or skin and melanoma in relation to PD. In the International Parkinson's Disease Genomic Consortium (IPDGC), we examined a broader selection of 360 pigmentation or melanoma GWAS SNPs in relation to PD among 5,333 PD cases and 12,019 controls. All participants were non-Hispanic Whites. As expected, in the PAGE study, most SNPs were associated with 1 or more pigmentation phenotypes. However, neither these SNPs nor pigmentation phenotypes were associated with PD risk after Bonferroni correction with the exception of rs4911414 at the ASIP gene (p = .001). A total of 18 PD cases (2.2%) and 26 controls (1.6%) had a diagnosis of melanoma with an odds ratio of 1.3 (95% confidence interval: 0.7-2.4). In the IPDGC analysis, none of the 360 SNPs, including rs4911414, were associated with PD risk after adjusting for multiple comparisons. In conclusion, we did not find significant associations between GWAS SNPs of pigmentation or melanoma and the risk for PD.
AU  - Dong, J.*
AU  - Gao, J.*
AU  - Nalls, M.*
AU  - Gao, X.*
AU  - Huang, X.*
AU  - Han, J.*
AU  - Singleton, A.B.*
AU  - Chen, H.*
AU  - International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T.
AU  - Lichtner, P.)
C1  - 31807
C2  - 34775
CY  - New York
SP  - 1512.e5-1512.e10
TI  - Susceptibility loci for pigmentation and melanoma in relation to Parkinson's disease.
JO  - Neurobiol. Aging
VL  - 35
IS  - 6
PB  - Elsevier Science Inc
PY  - 2014
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - A recent genome-wide association study (GWAS) found significant association of six single nucleotide polymorphisms (SNPs) in the gene FLJ10986 with sporadic amyotrophic lateral sclerosis (SALS). Another independent GWAS reported significant association of one SNP in the gene inositol 1,4,5-triphosphate receptor 2 (ITPR2) with SALS. These studies provided conflicting results. We examined the six most significant SNPs in FLJ10986 and one SNP in ITPR2 in a large cohort consisting of 595 SALS cases and 681 controls ascertained from Germany. Our results did not provide evidence for the association of these SNPs with SALS, suggesting a possible population-specific effect for FLJ10986 and ITPR2 that do not modulate the risk for SALS in the German population.
AU  - Fernández-Santiago, R.*
AU  - Sharma, M.*
AU  - Berg, D.*
AU  - Illig, T.
AU  - Annese, J.*
AU  - Meyer, T.*
AU  - Ludolph, A.*
AU  - Gasser, T.*
C1  - 5168
C2  - 28272
SP  - 551.e1-551.e4
TI  - No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort.
JO  - Neurobiol. Aging
VL  - 32
IS  - 3
PB  - Elsevier
PY  - 2011
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Sepiapterin reductase (SPR) gene is an enzyme which catalyses the final step of tetrahydrobiopterin synthesis (BH4) and was implicated in Parkinson's disease (PD) pathogenesis as a candidate gene for PARK3 locus. A number of studies yielded association of the PARK3 locus with PD, and SPR knockout mice were shown to display parkinsonian features. To evaluate the role of SPR gene polymorphisms in diverse populations in PD, we performed collaborative analyses in the Genetic Epidemiology of Parkinson Disease (GEO-PD) Consortium. A total of 5 single nucleotide polymorphisms (3 in the promoter region and 2 in the 3' untranslated region [UTR]) were genotyped. Fixed as well as random effect models were used to provide summary risk estimates of SPR variants. A total of 19 sites provided data for 6547 cases and 9321 controls. Overall odds ratio estimates varied from 0.92 to 1.01. No overall association with the SPR gene using either fixed effect or random effect model was observed in the studied population. I(2) Metric varied from 0% to 36.2%. There was some evidence for an association for participants of North European/Scandinavian descent with the strongest signal for rs1876487 (odds ratio = 0.82; p value = 0.003). Interestingly, families which were used to map the PARK3 locus, have Scandinavian ancestry suggesting a founder effect. In conclusion, this large association study for the SPR gene revealed no association for PD worldwide. However, taking the initial mapping of the PARK3 into account, the role of a population-specific effect warrants consideration in future studies.
AU  - Sharma, M.*
AU  - Maraganore, D.M.*
AU  - Ioannidis, J.P.*
AU  - Riess, O.*
AU  - Aasly, J.O.*
AU  - Annesi, G.*
AU  - Abahuni, N.*
AU  - Bentivoglio, A.R.*
AU  - Brice, A.*
AU  - van Broeckhoven, C.*
AU  - Chartier-Harlin, M.C.*
AU  - Destée, A.*
AU  - Djarmati, A.*
AU  - Elbaz, A.*
AU  - Farrer, M.*
AU  - Ferrarese, C.*
AU  - Gibson, J.M.*
AU  - Gispert, S.*
AU  - Hattori, N.*
AU  - Jasinska-Myga, B.*
AU  - Klein, C.*
AU  - Lesage, S.*
AU  - Lynch, T.*
AU  - Lichtner, P.
AU  - Lambert, J.C.*
AU  - Lang, A.E.*
AU  - Mellick, G.D.*
AU  - de Nigris, F.*
AU  - Opala, G.
AU  - Quattrone, A.*
AU  - Riva, C.*
AU  - Rogaeva, E.*
AU  - Ross, O.A.*
AU  - Satake, W.*
AU  - Silburn, P.A.*
AU  - Theuns, J.*
AU  - Toda, T.*
AU  - Tomiyama, H.*
AU  - Uitti, R.J.*
AU  - Wirdefeldt, K.*
AU  - Wszolek, Z.*
AU  - Gasser, T.*
AU  - Krüger, R*
AU  - Genetic Epidemiology of Parkinson's Disease Consortium (*)
C1  - 6758
C2  - 29214
SP  - 2108.e1-2108.e5
TI  - Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease.
JO  - Neurobiol. Aging
VL  - 32
IS  - 11
PB  - Elsevier
PY  - 2011
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - The aetiology of the selective neurodegeneration in Parkinson's disease (PD) is still unknown. Neurotrophic factors, e.g. glial cell line-derived neurotrophic factor (GDNF), have been shown to promote survival of dopaminergic neurons. Interestingly, aged mice lacking GDNF-receptor (RET) in their dopaminergic neurons show a phenotype similar to presymptomatic PD. We therefore were interested whether polymorphisms in the RET gene were associated with increased PD risk. Analyzing 25 SNPs in the RET region in 340 Southern German PD patients and 340 age- and sex-matched controls from Southern Germany (KORA S4), we did not find any significant association with PD, suggesting that the equilibrium of trophic factors in PD might be disturbed on other levels than the genomic encoding.
AU  - Lücking, C.B.*
AU  - Lichtner, P.
AU  - Kramer, E.R.*
AU  - Gieger, C.
AU  - Illig, T.*
AU  - Dichgans, M.*
AU  - Berg, D.*
AU  - Gasser, T.*
C1  - 1478
C2  - 27544
SP  - 167-168
TI  - Polymorphisms in the receptor for GDNF (RET) are not associated with Parkinson's disease in Southern Germany.
JO  - Neurobiol. Aging
VL  - 31
IS  - 1
PB  - Elsevier
PY  - 2010
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease with typical motor symptoms due to the preferential loss of midbrain dopaminergic (mDA) neurons in the Substantia nigra pars compacta. Several proteins of the homeodomain family are crucial for the development of mDA neurons. These proteins remain expressed into adulthood with largely unknown functions, but potentially influence mDA neuronal survival. To determine whether genetic variation in these genes plays a role in sporadic PD, we performed a genetic association study in a screening sample of 340 PD patients and 680 controls and a large replication sample of 669 PD patients and 669 controls using 54 single nucleotide polymorphisms in and around the Engrailed 1/2, PITX3, LMX1B and OTX2 genes. We provide evidence for a novel, strong and reproducible association of the PITX3 promoter SNP rs3758549: C > T (p = 0.004) with PD. The C-allele appears to be a recessive risk allele with an estimated population frequency of 83%. An allele-dependent dysregulation of PITX3 expression might contribute to the susceptibility to PD.
AU  - Fuchs, J.*
AU  - Mueller, J.C.*
AU  - Lichtner, P.
AU  - Schulte, C.*
AU  - Münz, M.*
AU  - Berg, D.*
AU  - Wüllner, U.*
AU  - Illig, T.
AU  - Sharma, M.*
AU  - Gasser, T.*
C1  - 2903
C2  - 26489
SP  - 731-738
TI  - The transcription factor PITX3 is associated with sporadic Parkinson's disease.
JO  - Neurobiol. Aging
VL  - 30
IS  - 5
PB  - Elsevier Science Inc.
PY  - 2009
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - A recently published whole genome association study showed the involvement of 13 SNPs in the pathogenesis of Parkinson disease (PD). We performed a replication study to assess their involvement in our sporadic cohort consisting of 663 cases and 1002 controls ascertained from Germany. One of the previously reported SNP, rs7723605, showed evidence of association (p value 0.04) in our sample. We further refined the signal by genotyping additional 22 SNPs around SNP rs7723605. Our refinement analysis, however, did not provide evidence for association in our sample after adjusting for multiple testing by permutation procedure. In conclusion, our study did not lend support to the finding that the reported SNPs are directly influencing the susceptibility to sporadic form of PD at least in our population.
AU  - Sharma, M.*
AU  - Lichtner, P.
AU  - Kruger, R.*
AU  - Berg, D.*
AU  - Schulte, C.*
AU  - Illig, T.
AU  - Riess, O.*
AU  - Gasser, T.*
C1  - 1604
C2  - 26898
CY  - New York
SP  - 1706-1709
TI  - Further delineation of the association signal on chromosome 5 from the first whole genome association study in Parkinson's disease.
JO  - Neurobiol. Aging
VL  - 30
IS  - 10
PB  - Elsevier Science
PY  - 2009
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - The supplementation of creatine (Cr) has a marked neuroprotective effect in mouse models of neurodegenerative diseases. This has been assigned to the known bioenergetic, anti-apoptotic, anti-excitotoxic, and anti-oxidant properties of Cr. As aging and neurodegeneration share pathophysiological pathways, we investigated the effect of oral Cr supplementation on aging in 162 aged C57Bl/6J mice. Outcome variables included "healthy" life span, neurobehavioral phenotyping, as well as morphology, biochemistry, and expression profiling from brain. The median healthy life span of Cr-fed mice was 9% higher than in control mice, and they performed significantly better in neurobehavioral tests. In brains of Cr-treated mice, there was a trend towards a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin. Expression profiling showed an upregulation of genes implicated in neuronal growth, neuroprotection, and learning. These data show that Cr improves health and longevity in mice. Cr may be a promising food supplement to promote healthy human aging.
AU  - Bender, A.*
AU  - Beckers, J.
AU  - Schneider, I.
AU  - Hölter, S.M.
AU  - Haack, T.B.*
AU  - Ruthsatz, T.
AU  - Vogt Weisenhorn, D.M.
AU  - Becker, L.
AU  - Genius, J.*
AU  - Rujescu, D.*
AU  - Irmler, M.
AU  - Mijalski, T.
AU  - Mader, M.T.
AU  - Quintanilla-Martinez, L.
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - Wurst, W.
AU  - Schmid, J.
AU  - Klopstock, T.
C1  - 3016
C2  - 25435
SP  - 1404-1411
TI  - Creatine improves health and survival of mice.
JO  - Neurobiol. Aging
VL  - 29
IS  - 9
PB  - Elsevier
PY  - 2008
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent. Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound differences in the biological functions of the encoded proteins, it is not possible to define a clinical phenotype distinguishing the disease caused by mutations in MAPT and PGRN genes.
AU  - Benussi, L.*
AU  - Binetti, G.*
AU  - Sina, E.*
AU  - Gigola, L.*
AU  - Bettecken, T.*
AU  - Meitinger, T.
AU  - Ghidoni, R.*
C1  - 3262
C2  - 25616
SP  - 427-435
TI  - A novel deletion in progranulin gene is associated with FTDP-17 and CBS.
JO  - Neurobiol. Aging
VL  - 29
IS  - 3
PB  - Elsevier
PY  - 2008
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - In Parkinson disease, wild-type alpha-synuclein accumulates during aging, whereas alpha-synuclein mutations lead to an early onset and accelerated course of the disease. The generation of new neurons is decreased in regions of neurogenesis in adult mice overexpressing wild-type human alpha-synuclein. We examined the subventricular zone/olfactory bulb neurogenesis in aged mice expressing either wild-type human or A53T mutant alpha-synuclein. Aging wild-type and mutant alpha-synuclein-expressing animals generated significantly fewer new neurons than their non-transgenic littermates. This decreased neurogenesis was caused by a reduction in cell proliferation within the subventricular zone of mutant alpha-synuclein mice. In contrast, no difference was detected in mice overexpressing the wild-type allele. Also, more TUNEL-positive profiles were detected in the subventricular zone, following mutant alpha-synuclein expression and in the olfactory bulb, following wild-type and mutant alpha-synuclein expression. The impaired neurogenesis in the olfactory bulb of different transgenic alpha-synuclein mice during aging highlights the need to further explore the interplay between olfactory dysfunction and neurogenesis in Parkinson disease.
AU  - Winner, B.*
AU  - Rockenstein, E.*
AU  - Lie, D.C.
AU  - Aigner, R.*
AU  - Mante, M.*
AU  - Bogdahn, U.*
AU  - Couillard-Despres, S.*
AU  - Masliah, E.*
AU  - Winkler, J.*
C1  - 2570
C2  - 25632
SP  - 913-925
TI  - Mutant alpha-synuclein exacerbates age-related decrease of neurogenesis.
JO  - Neurobiol. Aging
VL  - 29
IS  - 6
PB  - Elsevier
PY  - 2008
SN  - 0197-4580
ER  - 

TY  - JOUR
AB  - Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.
AU  - Mueller, J.C.*
AU  - Riemenschneider, M.*
AU  - Schoepfer-Wendels, A.*
AU  - Gohlke, H.
AU  - Konta, L.*
AU  - Friedrich, P.*
AU  - Illig, T.
AU  - Laws, S.*
AU  - Förstl, H.*
AU  - Kurz, A.
C1  - 3957
C2  - 24610
SP  - 727-734
TI  - Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.
JO  - Neurobiol. Aging
VL  - 28
IS  - 5
PB  - Elsevier
PY  - 2007
SN  - 0197-4580
ER  - 

TY  - JOUR
AU  - Gohlke, H.
AU  - Illig, T.
AU  - Klopp, N.
AU  - Wagenpfeil, S.*
AU  - Konta, L.*
AU  - Laws, S.M.*
AU  - Kurz, A.*
AU  - Riemenschneider, M.*
C1  - 3291
C2  - 23796
SP  - 776.e1-776.e3
TI  - Association study between the D10S1423 microsatellite marker and Alzheimer's disease.
JO  - Neurobiol. Aging
VL  - 27
PY  - 2006
SN  - 0197-4580
ER  - 

TY  - JOUR
AU  - Riemenschneider, M.*
AU  - Mahmoodzadeh, S.*
AU  - Eisele, T.*
AU  - Klopp, N.
AU  - Schwarz, S.*
AU  - Wagenpfeil, S.*
AU  - Diehl, J.*
AU  - Mueller, U.*
AU  - Foerstl, H.*
AU  - Illig, T.
AU  - Kurz, A.*
C1  - 2507
C2  - 22186
SP  - 1305-1308
TI  - Association analyis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease.
JO  - Neurobiol. Aging
VL  - 25
PY  - 2004
SN  - 0197-4580
ER  -