Background: Cerebral amyloid angiopathy (CAA) is classified as type 1 with capillary amyloid β (Aβ) or type 2 without capillary Aβ. While it is known that CAA activates complement, an inflammatory mediator, there is no information on the relationship between capillary Aβ and complement activation. Methods: We evaluated 34 autopsy brains, including 22 with CAA and 12 with other neurodegenerative diseases. We assessed the vascular density of CAA by analyzing the expression of complement (C1q, C3d, C6, C5b-9), macrophage scavenger receptor (MSR), and apolipoprotein E (ApoE). Results: Capillary immunostaining for C1q, C3d, MSR, and ApoE was identified almost exclusively in CAA-type1 brains. There was intense expression of C1q, C3d, MSR, and ApoE, as well as weaker expression of C5b-9 and C6 in the arteries/ arterioles of both CAA subtypes, but not in control brains. C5b-9 and C6 were preferentially expressed in arteries/arterioles with subcortical hemorrhage or cortical superficial siderosis. Triple immunofluorescence revealed that C1q, C3d, and ApoE were colocalized with Aβ in CAA brain capillaries. Conclusion: Complement, MSR, and ApoE were only coexpressed in the presence of Aβ accumulation in capillaries, suggesting a role for complement activation in the propagation of Aβ. Additionally, C5b-9 expression may be associated with hemorrhagic brain injury in CAA.

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer’s disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.

Vaccination is the easiest way to stimulate the immune system to confer protection from disease. However, the inefficacy of vaccination in the elderly, especially those under nutritional control such as individuals receiving artificial nutrition after cerebral infarction or during dementia, has led to the search for an adjuvant to augment the acquired immune response in this population. The cross-talk between the gut microbiota and the host immune system is gaining attention as a potential adjuvant for vaccines. Probiotics, prebiotics, and postbiotics, which are commonly used to modulate gut health, may enhance the immune response and the effectiveness of vaccination in the elderly. This review summarizes the use of these gut modulators as adjuvants to boost both the innate and acquired immune responses in the elderly under nutritional control. Although the clinical evidence on this topic is limited and the initial findings await clarification through future studies with large sample sizes and proper study designs, they highlight the necessity for additional research in this field, especially in light of the ongoing COVID-19 pandemic, which is disproportionately affecting the elderly.

We investigated the effect of a formula containing two different prebiotics (bifidogenic growth stimulator and galacto-oligosaccharide) and fermented milk products on intestinal microbiota and antibody responses to an influenza vaccine in enterally fed elderly in-patients. Patients were administered either formula containing prebiotics and fermented milk products (group F: n = 12, 79.9 ± 9.5 years old) or standard formula (group C: n = 12, 80.7 ± 10.1 years old) via percutaneous endoscopic gastrostomy during a 14-week intervention period. Subjects were immunized with an influenza vaccine (A/H1N1, A/H3N2, and B) at week 4 of the intervention. Blood biochemical indices, intestinal bacteria populations and antibody titers were analyzed. Bifidobacterium counts increased significantly in group F compared with group C. The enhanced antibody titers against A/H1N1 were maintained in group F for a longer period compared with group C. The titers against A/H3N2 were unchanged between both groups, and those against B were significantly lower in group F than in group C, although few subjects had seroprotective titers against A/H3N2 and B. These results suggest that administration of the formula containing prebiotics and fermented milk products may maintain antibody titers for longer periods through the improvement of intestinal microbiota.