👤 Lauren E Salminen

Ambient air pollution exposures increase risk for Alzheimer's disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, previous MRI studies examining exposure effects on the MTL were cross-sectional and mostly focused on the hippocampus, yielding mixed results. We addressed these limitations using longitudinal data collected from 653 cognitively unimpaired community-dwelling women from the Women's Health Initiative Memory Study with two MRI scans (M Show less

Small dense low-density lipoprotein (sdLDL) is atherogenic and associated with atherosclerotic cardiovascular diseases (ASCVD). The aim of this study was to perform the prospective evaluation of sdLDL-c in new ASCVD over 18 years of follow up, and to compare the association of sdLDL-c and conventional lipids and apolipoproteins with ASCVD in the elderly. This prospective study included a total of 1770 subjects ≥ 64 years of age with an 18-year follow-up period. The determination of sdLDL-c was measured by a homogenous, selective enzymatic method. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined by enzymatic methods. Apolipoproteins, ApoA1 and ApoB, were analyzed by immunonephelometric methods. Low-density lipoprotein cholesterol (LDL-c) levels were calculated using the Friedewald formula. According to Pearson's correlation coefficients, sdLDL-c concentration was positively correlated with LDL-c, nonHDL-c, TC and ApoB concentrations. During follow up, sdLDL-c was significantly associated with new ASCVD in men aged 64-76 years in both unadjusted and adjusted Cox regression models. The adjusted hazard ratio (95 % CI) for sdLDL-c was 1.61 (1.13-2.28). No significant associations between sdLDL-c and ASCVD were observed in men aged 77-97 years, nor in women aged 64-79 or 80-100 years. Lipid and apolipoprotein concentrations of the elderly were high compared to the recommended target values. In addition, lipid and apolipoprotein baseline concentrations were not higher in the ASCVD group than in the control group. Our results indicated that sdLDL-c is as good a marker as ApoB and better than LDL-c. Show less

The accumulation of amyloid-β-containing neuritic plaques and intracellular tau protein tangles are key histopathological hallmarks of Alzheimer's disease (AD). This type of pathology clearly indicates that the mechanisms of neuronal housekeeping and protein quality control are compromised in AD. There is mounting evidence that the autophagosome-lysosomal degradation is impaired, which could disturb the processing of APP and provoke AD pathology. Beclin 1 is a molecular platform assembling an interactome with stimulating and suppressive components which regulate the initiation of the autophagosome formation. Recent studies have indicated that the expression Beclin 1 is reduced in AD brain. Moreover, the deficiency of Beclin 1 in cultured neurons and transgenic mice provokes the deposition of amyloid-β peptides whereas its overexpression reduces the accumulation of amyloid-β. There are several potential mechanisms, which could inhibit the function of Beclin 1 interactome and thus impair autophagy and promote AD pathology. The mechanisms include (i) reduction of Beclin 1 expression or its increased proteolytic cleavage by caspases, (ii) sequestration of Beclin 1 to non-functional locations, such as tau tangles, (iii) formation of inhibitory complexes between Beclin 1 and antiapoptotic Bcl-2 proteins or inflammasomes, (iv) interaction of Beclin 1 with inhibitory neurovirulent proteins, e.g. herpex simplex ICP34.5, or (v) inhibition of the Beclin 1/Vps34 complex through the activation of CDK1 and CDK5. We will shortly introduce the function of Beclin 1 interactome in autophagy and phagocytosis, review the recent evidence indicating that Beclin 1 regulates autophagy and APP processing in AD, and finally examine the potential mechanisms through which Beclin 1 dysfunction could be involved in the pathogenesis of AD. Show less