Multiple BACE1 inhibitors abnormally increase the BACE1 protein level in neurons by prolonging its half-life.
DISCUSSION: Elevation of BACE1 by 7 of 8 BACE1 inhibitors raises new concerns about advancing such β-secretase inhibitors for AD. Chronic elevation could lead to intermittently uninhibited BACE1 when orally dosed inhibitors reach trough levels, abnormally increasing substrate processing. Compounds such as roburic acid that lower Aβ by dissociating β/γ secretase complexes are better candidates because they neither inhibit β- and γ-secretase nor increase BACE1 levels. PMID: 31416794 [PubMed - as supplied by publisher]
CONCLUSIONS: Our data indicate that acute exposure to a strong IMO stressor, composed of the combined physical and psychological challenges, induces similar inflammatory and other ADrelated neuropathological changes as the immune LPS treatment. Our data also indicate that cytokines are most likely released from the peripheral immune cells, as we detected myeloid cells activity, without any microglia response. We hypothesize that stress induces innate immune response in the brain that consequently potentiate the expression of genes implicated in the AD-related neuropathology. PMID: 31517627 [PubMed - in process]
Publication date: Available online 13 September 2019Source: Biosensors and BioelectronicsAuthor(s): Kai Zhang, Qianlu Yang, Zhenqiang Fan, Jianfeng Zhao, Hao LiAbstractSoft material fabricated with DNA origami or peptide cross-linking technique may be promising theranostic platforms in the future; however, their naturally occurring counterparts, such as the peptide aggregates in the neurodegenerative diseases, constitute an increasingly burdensome issue of public health. Thus, a design of artificial peptide nano-network biosensor is conceived, in an attempt to combat the natural pathological peptides, by mimicking their pa...
CONCLUSIONS: Atrophy of the DGM structures, especially the thalamus and caudate nucleus, is related to cognitive impairment in AD. DGM atrophy is associated with tests reflecting both subcortical and cortical cognitive functions. PMID: 31514198 [PubMed - as supplied by publisher]
DISCUSSION: Poor performance on several independent gait domains precedes cognitive decline and incident dementia. PMID: 31515066 [PubMed - as supplied by publisher]
DISCUSSION: Data demonstrate that ASD behaviors may seem de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies. PMID: 31517641 [PubMed - as supplied by publisher]
CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases. PMID: 31513029 [PubMed - as supplied by publisher]
Publication date: Available online 13 September 2019Source: The Lancet NeurologyAuthor(s): Ingrid S van Maurik, Stephanie J Vos, Isabelle Bos, Femke H Bouwman, Charlotte E Teunissen, Philip Scheltens, Frederik Barkhof, Lutz Frolich, Johannes Kornhuber, Jens Wiltfang, Wolfgang Maier, Oliver Peters, Eckart Rüther, Flavio Nobili, Giovanni B Frisoni, Luiza Spiru, Yvonne Freund-Levi, Asa K Wallin, Harald Hampel, Hilkka SoininenSummaryBackgroundBiomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifyin...
ConclusionRecognition of emotional stimuli was more accurate compared to non-emotional stimuli in AD, left-sided PD and HC; right-sided PD did not show sensitivity to the emotional valence of the stimuli suggesting the involvement of the nigrostriatal, mesocortical and mesolimbic circuitry of the left hemisphere in the emotional-reward system related to the aesthetic experience.
In conclusion, our findings showed that a dherence to healthy diet can decrease oxidative stress and inflammation and accumulation of amyloid-β and consequently can decrease the risk of AD.
We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigg...