However, recent insight from mouse models of KD/SBMA have suggested that primary myogenic pathology, and more specifically pathological alterations in gene expression within skeletal muscle, might also contribute to this disease (reviewed in [5]).
This suggests, as in the other loci above, that nongenetic factors may be influencing AD pathology through alterations in DNA methylation which can manifest as alterations in transcriptional patterns.
This is significant, as Huntington's disease shares several similarities with KD/SBMA: it is also caused by polyglutamine expansion mutations [4], and neuromuscular pathology, including alterations in skeletal muscle gene expression are observed in mouse models of this disease [29], [45].
Perfusion parameters are of interest since changes in vascularity and blood flow secondary to pathology generate alterations in the time intensity curve [ 16].
Beyond extending our understanding of neuronal function and pathology, the alterations in channel conductance can now be targeted with specific drugs so as to point to new directions in therapy of cognitive disabilities of DS.
Experimental data also highlight the potential importance of genes involved in these processes in AD pathology, with alterations in lipid and cholesterol levels having been observed in the blood, cerebrospinal fluid, and brains of patients with AD [ 87, 88], and associated with cognitive performance [ 89].
The results presented here indicate that EC neurons from mice genetically programmed to develop extensive Aβ and tau pathologies display alterations of intrinsic properties consistent with reduced membrane surface (atrophy) and show increased neuronal activity.
Interestingly, with regard to α-synuclein (αS) pathology, the alteration in the predictable progressions of pathology has been proposed to be due to concomitant AD pathology (16, 22).
In addition to dissimilar age and pathologies, also alterations of creatinine clearance and the fact that U-LTE4 was measured using different techniques (ELISA versus liquid chromatographic tandem mass spectrometry) could contribute to higher creatinine-normalized U-LTE4 concentrations in the present study.
