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0521 / 0.8337). In calf muscles mDTI showed significant differences between DM 1 and DM 2 patients (all p < 0.0001) as well as between DM 1 patients and controls (all p = 0.0001). Thigh muscles had a significant higher fat-fraction in both groups vs. controls (p < 0.05). There was no correlation of CTG triplet length with mDTI values and fat-fraction.

mDTI reveals specific changes of the diffusion parameters and fat-fraction in muscles of DM 1 and DM 2 patients. Thus, the quantitative MRI methods presented in this study provide a powerful tool in differential diagnosis and follow-up of DM 1 and DM 2, however, the data must be validated in larger studies.

mDTI reveals specific changes of the diffusion parameters and fat-fraction in muscles of DM 1 and DM 2 patients. Thus, the quantitative MRI methods presented in this study provide a powerful tool in differential diagnosis and follow-up of DM 1 and DM 2, however, the data must be validated in larger studies.

Huntington's disease (HD) is caused by an expanded (>35) CAG trinucleotide repeat in huntingtin (HTT). Age-at-onset of motor symptoms is inversely correlated with the size of the inherited CAG repeat, which expands further in brain regions due to somatic repeat instability. Our recent genetic investigation focusing on autosomal SNPs revealed that age-at-onset is also influenced by genetic variation at many loci, the majority of which encode genes involved in DNA maintenance/repair processes and repeat instability.

We performed a complementary association analysis to determine whether variants in the X chromosome modify HD.

We imputed SNPs on chromosome X for ∼9,000 HD subjects of European ancestry and performed an X chromosome-wide association study (XWAS) to test for association with age-at-onset corrected for inherited CAG repeat length.

In a mixed effects model XWAS analysis of all subjects (males and females), assuming random X-inactivation in females, no genome-wide significant onset modificatpathway analysis, and data download.

Abnormal default mode network (DMN) was associated with the progress of Alzheimer's disease (AD). Rather than treat the DMN as a unitary network, it can be further divided into three subsystems with different functions.

It remains unclear the interactions of DMN subsystems associated with the progress of cognitive impairments and AD pathological features.

This study has recruited 187 participants, including test data and verification data. Firstly, an imaging analysis approach was utilized to investigate disease-related differences in the interactions of DMN subsystems in test data (n = 149), including 42 cognitively normal subjects, 43 early mild cognitive impairment (EMCI), 32 late mild cognitive impairment (LMCI), and 32 AD patients. Brain-behavior-pathological relationships regarding to the interactions among DMN subsystems were then further examined. Secondly, DMN subsystems abnormalities for classifying AD spectrum population in the independent verification data (n = 38).

This study found that tevelopment of AD.

The locus coeruleus (LC), a brainstem nucleus comprising noradrenergic neurons, is one of the earliest regions affected by Alzheimer's disease (AD). Amyloid-β (Aβ) pathology in the cortex in AD is thought to exacerbate the age-related loss of LC neurons, which may lead to cortical tau pathology. However, mechanisms underlying LC neurodegeneration remain elusive.

Here, we aimed to examine how noradrenergic neurons are affected by cortical Aβ pathology in AppNL-G-F/NL-G-F knock-in mice.

The density of noradrenergic axons in LC-innervated regions and the LC neuron number were analyzed by an immunohistochemical method. To explore the potential mechanisms for LC degeneration, we also examined the occurrence of tau pathology in LC neurons, the association of reactive gliosis with LC neurons, and impaired trophic support in the brains of AppNL-G-F/NL-G-F mice.

We observed a significant reduction in the density of noradrenergic axons from the LC in aged AppNL-G-F/NL-G-F mice without neuron loss or tau pathology, which was not limited to areas near Aβ plaques. However, none of the factors known to be related to the maintenance of LC neurons (i.e., somatostatin/somatostatin receptor 2, brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) were significantly reduced in AppNL-G-F/NL-G-F mice.

This study demonstrates that cortical Aβ pathology induces noradrenergic neurodegeneration, and further elucidation of the underlying mechanisms will reveal effective therapeutics to halt AD progression.

This study demonstrates that cortical Aβ pathology induces noradrenergic neurodegeneration, and further elucidation of the underlying mechanisms will reveal effective therapeutics to halt AD progression.

Accumulation of iron is a consistent feature of Alzheimer's disease (AD) brains. The underlying cause, however, remains debatable.

To explore whether local hepcidin synthesized by brain cells contributes to iron accumulation in AD brains.

Brain tissue from the cingulate cortex of 33 cases of AD pre-assigned to Braak stage I-VI, 6 cases of non-dementia, and 15 cases of non-AD dementia were analyzed for transcriptional upregulation of hepcidin by RT-qPCR and RT-PCR. Change in the expression of ferritin, ferroportin (Fpn), microglial activation marker Iba1, IL-6, and TGFβ2 was determined by western blotting. Total tissue iron was determined by colorimetry.

Significant transcriptional upregulation of hepcidin was observed in Braak stage III-VI relative to Braak stage I and II, non-AD dementia, and non-dementia samples. Cpd 20m order Ferritin was increased in Braak stage V, and a significant increase in tissue iron was evident in Braak stage III-VI. The expression of Iba1 and IL-6 was also increased in Braak stage III-VI relative to Braak stage I and II and non-AD dementia samples. Amyloid-β plaques were absent in most Braak stage I and II samples, and present in Braak stage III-VI samples with few exceptions.

These observations suggest that upregulation of brain hepcidin is mediated by IL-6, a known transcriptional activator of hepcidin. The consequent downregulation of Fpn on neuronal and other cells results in accumulation of iron in AD brains. The increase in hepcidin is disease-specific, and increases with disease progression, implicating AD-specific pathology in the accumulation of iron.

These observations suggest that upregulation of brain hepcidin is mediated by IL-6, a known transcriptional activator of hepcidin. The consequent downregulation of Fpn on neuronal and other cells results in accumulation of iron in AD brains. The increase in hepcidin is disease-specific, and increases with disease progression, implicating AD-specific pathology in the accumulation of iron.