Understanding mental disorders from neuronal networks to glial cells and proteomics

Dement Geriatr Cogn Disord

Guo²,

Kratzer³

et al. 2011

ciations between CSF A ␤ 1-42 levels and the SORL1 SNPs 23 (rs3824968) and 24 (rs2282649) were detected in the AD group. The latter association became marginally statistically insignificant after Bonferroni correction for multiple comparisons. Carriers of the SORL1 SNP24 T allele and the SNP23 A allele both had lower CSF A ␤ 1-42 concentrations than noncarriers of these alleles. The analysis of the impact of interactions between APOE 4 allele and SORL1 SNPs on CSF A ␤ 1-42 levels unraveled significant influences of APOE . Conclusions: Our findings provide further support for the notion that SORL1 genetic variants are related to AD pathology, probably by regulating the amyloid cascade.Copyright © 2011 S. Karger AG, Basel Key WordsDementia ؒ Mild cognitive impairment ؒ Healthy aging ؒ Amyloid cascade ؒ Association Abstract Background: Recently, genetic variants of the neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) have emerged as risk factors for the development of Alzheimer's disease (AD). Methods: In this study, SORL1 gene polymorphisms, which have been shown to be related to AD, were analyzed for associations with cerebrospinal fluid (CSF) amyloid beta1-42 (A ␤ 1-42 ), phosphorylated tau181, and total tau levels in a non-Hispanic Caucasian sample, which encompassed 100 cognitively healthy elderly individuals, 166 patients with mild cognitive impairment, and 87 patients with probable AD. The data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). Moreover, the impact of gene-gene interactions between SORL1 single nucleotide polymorphisms (SNPs) and the apolipoprotein E (APOE) 4 allele, the major genetic risk factor for sporadic AD, on A ␤ 1-42 concentrations was investigated. Results: Significant asso-

“…Therefore, our results provide further in vivo validation of SORL1 as a risk gene for AD and stress the need for subsequent studies to unveil its pathogenic and clinical relevance [44] .…”

Section: Discussionmentioning

confidence: 99%

Impact of SORL1 Single Nucleotide Polymorphisms on Alzheimer’s Disease Cerebrospinal Fluid Markers

Dement Geriatr Cogn Disord

Guo²,

Kratzer³

et al. 2011

“…Progress in the field of AD biomarkers [10,25] enabled a workgroup of the National Institute on Aging and the Alzheimer's Association (NIA-AA) to develop a novel set of clinical criteria for MCI. MCI-core clinical criteria for healthcare providers without access to advanced imaging techniques or cerebrospinal fluid (CSF) analyses were proposed in addition to research criteria incorporating biomarkers, which were recommended for clinical research settings including clinical trials [1].…”

Section: Introductionmentioning

confidence: 99%

The National Institute on Aging-Alzheimer’s Association research criteria for mild cognitive impairment due to Alzheimer’s disease: predicting the outcome

Guo

Eur Arch Psychiatry Clin Neurosci

Eisele

et al. 2012

The National Institute on Aging-Alzheimer's Association (NIA-AA) clinical research criteria for mild cognitive impairment (MCI) due to Alzheimer's disease (AD) incorporate the use of biomarkers to classify patients according to the likelihood of the presence of AD pathology. The aim of the study was to compare the risk of progression to AD dementia between the four NIA-AA MCI subgroups using data from the AD Neuroimaging Initiative. Patients with MCI were categorised according to the NIA-AA criteria into subgroups with high, intermediate, and low likelihood of the presence of AD pathology (MCI-high, MCI-intermediate, and MCI-unlikely, respectively) or into a group of patients that only met the MCI-core clinical criteria (MCI-core). Data of follow-up visits conducted 6-60 months after baseline were used to compare the relative risk of future AD dementia between the four subgroups employing a Cox regression model. The MCI-high subgroup (N = 22) had a 2.3 times higher risk of developing AD dementia compared with the MCI-core subgroup (N = 327; P = 0.002), while there was a trend for a higher risk in the MCI-high subgroup in contrast to the MCI-intermediate subgroup (N = 31, P = 0.08). No patients in the MCI-unlikely subgroup (N = 17) progressed to AD dementia. Patients with MCI-high have a higher risk for developing AD dementia. The new NIA-AA MCI criteria represent a valuable research instrument that could be incorporated into the diagnostic process of the MCI syndrome after optimisation and refinement.

Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI

Eur Arch Psychiatry Clin Neurosci

Sorg

Förschler

et al. 2011

110

Alzheimer's disease (AD) and mild cognitive impairment (MCI), the transitional clinical stage between cognition in normal aging and dementia, have been linked to abnormalities in brain perfusion. Pulsed arterial spin labeling (PASL) is a magnetic resonance imaging (MRI) technique for evaluating brain perfusion. The present study aimed to determine regional perfusion abnormalities in 19 patients with mild dementia in AD and 24 patients with MCI as compared to 24 cognitively healthy elderly controls using PASL. In line with nuclear imaging methods, lower perfusion in patients with MCI and AD was found mainly in the parietal lobe, but also in angular and middle temporal areas as well as in the left middle occipital lobe and precuneus. Our data imply that PASL may be a valuable instrument for investigating perfusion changes in the transition from normal aging to dementia and indicate that it might become an alternative to nuclear imaging techniques in AD diagnostics.