Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as A a a b c-predominant age-related TDP-43 encephalopathy (LATE).There may also be complex physiologic interactions between metabolic syndrome (e.g. hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that include consideration of comorbid diseases, B-ASC is independently associated with impairments in global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Ultraviolet (UV-C) irradiation is a non-thermal disinfection method, effective against a range of bacteria and viruses, which is being considered as an alternative to pasteurization of fruit juices. The objective of this study was to investigate the effect of UV-C irradiation on the polyphenolic content and in-vitro total antioxidant activity of apple juice. UV irradiation doses ranging from 0 to 240 mJ•cm-2 were delivered to apple juice and polyphenols, sugars, in-vitro total antioxidant activity and total phenols were profiled. The results demonstrated that UV-C irradiation in apple juices at relevant commercial disinfection doses induced significant reduction in the concentrations of chlorogenic acid, phloridzin, and epicatechin (p<0.05). The induced changes were relatively minor for the above mentioned polyphenols, except phloridzin (50% reduction) at 240 mJ•cm-2. Epicatechins concentrations were reduced significantly (p<0.05), whereas increase in catechins concentration was observed with increase in UV-C exposure to 240 mJ•cm-2. There was a minor reduction in sugars (glucose and fructose) concentrations with increasing exposure levels from 0-40 mJ•cm-2 (p>0.05). In contrast, a slight increase in sugars concentrations as increase in UV exposure after 40 mJ•cm-2 was observed. These changes were not significantly different from control. Total phenolic content was well retained regardless of the UV exposure for apple juice. In-vitro total antioxidant activity changed when UV exposure exceeded 40 mJ•cm-2 , but remained unchanged at the maximum UV dose of 240 mJ•cm-2. These results suggested that UV-C irradiation could be an effective alternative to conventional thermal processing for production of high quality apple juice. Industrial Relevance This research paper provides scientific evidence of the potential for UV-C irradiation to achieve meaningful levels of disinfection while retaining important bioactive compounds (polyphenols) in apple juice. In-vitro antioxidant activity and individual polyphenols were well retained at commercially relevant doses of 40 mJ•cm-2. From a nutritional perspective, UV-C irradiation is an attractive food preservation technology and offers opportunities for horticultural and food processing industries to meet the growing demand from consumers for healthier food products. Therefore, UV-C irradiated foods could be sold at a premium price to their thermally-processed counterparts, as they have retained their fresh-like properties. This study would provide technical information relevant for commercialization of UV-C treatment of juices.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory and the Rush Aging Project (ROSMAP; n = 780 included) were analyzed in the current study. Our goals were to reevaluate disease-associated genetic variants using newly collected data and to query whether the specific genotype/phenotype associations could provide new insights into disease-driving pathways. Research subjects included in prior LATE/HS genome-wide association studies (GWAS) were excluded. Single nucleotide variants (SNVs) within 10 kb of TMEM106B, GRN, ABCC9, KCNMB2, and APOE were tested for association with HS and LATE-NC, and separately for Alzheimer’s pathologies, i.e. amyloid plaques and neurofibrillary tangles. Significantly associated SNVs were identified. When results were meta-analyzed, TMEM106B, GRN, and APOE had significant gene-based associations with both LATE and HS, whereas ABCC9 had significant associations with HS only. In a sensitivity analysis limited to LATE-NC + cases, ABCC9 variants were again associated with HS. By contrast, the associations of TMEM106B, GRN, and APOE with HS were attenuated when adjusting for TDP-43 proteinopathy, indicating that these genes may be associated primarily with TDP-43 proteinopathy. None of these genes except APOE appeared to be associated with Alzheimer’s-type pathology. In summary, using data not included in prior studies of LATE or HS genomics, we replicated several previously reported gene-based associations and found novel evidence that specific risk alleles can differentially affect LATE-NC and HS.

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