Highlights d Aging leads to the most profound changes in brain gene expression networks d Immune module led by Alzheimer's risk genes Trem2/Tyrobp is upregulated with aging d Alzheimer's risk allele APOE4 increases the expression of Serpina3 family genes d Alzheimer's protective allele APOE2 drives unique serum metabolome profiles
Maximal voluntary tongue pressure is decreased in Japanese frail elderly personsBackground and objective: To quantitatively estimate tongue function, we developed a handy device for intraoral pressure measurement. The objective of this study was to assess maximum voluntary tongue pressure (MVTP) in Japanese frail elderly persons receiving nursing care services. Materials and methods: The study included 42 men and 87 women, aged 58-100 years. To record MVTP, the participants were asked to compress the balloon (diameter: 18 mm) of the disposable intraoral pressure probe onto their palates for 7 s using the maximum voluntary effort of the tongue. Pressures were recorded three times at 1 min intervals. Results: Maximum voluntary tongue pressure was successfully measured in 111 persons. Mean (standard deviation) MVTP was 18 (12) kPa, with a range of 0-63 kPa. The remaining 18 persons could not accurately follow our instructions and MVTP could not be measured. Conclusion: In comparison with the reported standard value using the same device, the frail elderly persons included in our study were found to exert less MVTP than healthy dentate individuals. These results suggest the need for proper quantitative evaluation of oral function, including tongue capacity, at nursing care facilities.
(GB). pathology (9). Thus, it is predicted that neuronal LRP1 deficiency also prevents apoE4-related Aβ aggregation at an early stage. One limitation of our study is that we could not analyze Aβ pathology in older mice due to a reduced survival rate at the age of 12 months, for unknown reasons. At older ages, neuronal LRP1 deficiency may accelerate Aβ deposition independently of apoE4. In this regard, suppressing LRP1 levels may not be a suitable approach as potential AD therapy because LRP1 plays a critical role in maintaining brain homeostasis (5, 10). Nonetheless, increasing apoE4 amounts in the TBS-X-soluble fraction may be an alternative therapeutic intervention for AD with APOE4. Modifying apoE4 solubility and/ or retaining more apoE4 onto the cell surface at an early stage of AD could potentially be beneficial, in addition to lowering the amount of apoE4 aggregates through treatment with specific antisense oligonucleotides (27) or antibodies (28). Taken together, our results indicate that exploring interactive roles of apoE and apoE receptors in Aβ metabolism would help us to better understand the mechanisms underlying the contribution of APOE4 to the risk of AD development and progression. Methods Study approval. The Mayo Clinic Institutional Review Board approved all protocols for human study in which experimental procedures were conducted. All subjects gave informed consent. The Mayo Clinic Institutional Animal Care and Use Committee approved
Introduction: Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer's disease (AD) cases. Methods: We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [A 40], A 42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA. Results: Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high A 40 levels, APOE 4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels. Discussion: Refining the molecular mechanisms connecting tau, A , and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease.
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