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INTRODUCTION: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH‐connected cortex using multimodal images. METHODS: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography. RESULTS: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18F‐SynVesT‐1 PET. In addition, higher ratios of Aβ in the deep WMH‐connected versus WMH‐unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH‐connected cortex reduced more than WMH‐unconnected cortex over 12 months. DISCUSSION: Our results suggest that WMH may be associated with AD‐intrinsic processes of degeneration, in addition to vascular mechanisms. Highlights: We studied white matter hyperintensities (WMHs) and WMH‐connected cortical changes.WMHs are associated with more severe regional cortical degeneration.Findings suggest WMHs may be associated with Alzheimer's disease–intrinsic processes of degeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-[beta] (A[beta]) in Alzheimer's disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. METHODS. sTREM2 and A[[beta].sub.1-42] levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and A[[beta].sub.1-42] levels were determined for our Neurology database of Ruijin Hospital for Alzheimer's Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) database. RESULTS. The results showed that patients with MCI who had low levels of CSF sTREM2 and A[[beta].sub.1-42] were more likely to develop AD. Among participants with positive A[beta] deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low A[[beta].sub.1-42] with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database. CONCLUSION. These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion. FUNDING. This study was supported by grants from the National Natural Science Foundation of China (grant nos. 82001341, 82071415, 81873778, and 82201392); the Shanghai Sailing Program (grant no. 22YF1425100); and the China Postdoctoral Science Foundation funded project (grant no. 2021M702169)., Introduction Triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor expressed in myeloid cells, plays an important role in regulating microglial phagocytosis and the response to inflammatory stimuli [...]

OBJECTIVE: To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. RESULTS: After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR [95% CI] per SD increment: 1.13 [1.03, 1.23]). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. CONCLUSIONS: A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD. [ABSTRACT FROM AUTHOR]

Based on the excellent comprehensive mechanical properties of high–entropy alloy (HEA), the NiAl-based HEA was designed to achieve excellent high-temperature strength, toughness, and wear resistance. In this work, vacuum arc melting technology was used to prepare (NiA1)78(CoCrFe)16.5Cu5.5 HEA, and its microstructure, phase composition, and mechanical properties were systematically studied. The results showed that (NiA1)78(CoCrFe)16.5Cu5.5 HEA was composed of FCC and BCC/B2, with a spinodal decomposition structure in the matrix, and nano-precipitation in the interdendritic, exhibiting a good high-temperature performance. At 600 °C, the compressive fracture strength is 842.5 MPa and the fracture strain is 24.5%. When the temperature reaches 800 °C, even if the strain reaches 50%, the alloy will not fracture, and the stress–strain curve shows typical work hardening and softening characteristics. The wear coefficient of the alloy first increases and then decreases with the increase in temperature in the range of room temperature to 400 °C. However, the specific wear rate shows the opposite trend. At 100 °C, the wear rate reaches the lowest of 7.05 × 10−5 mm3/Nm, and the wear mechanism is mainly abrasive wear. [ABSTRACT FROM AUTHOR]

The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer's disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD. [ABSTRACT FROM AUTHOR]

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer’s disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case–control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim<0.0001) while haplotype C-C-A-T-C, C-C-A-C-C, T-T-A-C-C were significantly lower (Psim<0.0001). Our data suggested that the genetic variation of the rs10884402 and rs950809 in intron 1 of SORCS1 was associated with the late-onset AD in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: We conducted a case-control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer's disease in Chinese Southern Han population. Methods: PCR-restriction fragment length polymorphism assay was performed to genotype rs75932628 in 279 cases with late onset Alzheimer's diseases patients and 346 control subjects in Shanghai and Nanjing. Results: There was no rs75932628-T variant detected in our sample. However, APOE&4 was shown closely associated with the risk of Alzheimer's disease (Chi-square=60.288, P= 0.000). Conclusion: Our study suggested that TREM2(rs75932628-T) was rare in Chinese Han population. Further association studies with large samples are needed to further study the association of TREM2 with late-onset Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH-connected cortex using multimodal images., Methods: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography., Results: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18 F-SynVesT-1 PET. In addition, higher ratios of Aβ in the deep WMH-connected versus WMH-unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH-connected cortex reduced more than WMH-unconnected cortex over 12 months., Discussion: Our results suggest that WMH may be associated with AD-intrinsic processes of degeneration, in addition to vascular mechanisms., Highlights: We studied white matter hyperintensities (WMHs) and WMH-connected cortical changes. WMHs are associated with more severe regional cortical degeneration. Findings suggest WMHs may be associated with Alzheimer's disease-intrinsic processes of degeneration., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)