Understanding the mechanisms behind Alzheimer’s disease (AD) and blood-brain barrier (BBB) dysfunction is like exploring a complex maze with multiple interconnected pathways. Just as a maze has various paths that can lead you astray or guide you to the correct exit, chronic vascular risk factors and AD biomarkers also contribute to the breakdown of BBB integrity. This recent study delved into the combined effects of these factors in a cohort of 95 dementia patients with different types of dementia. By measuring the cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, the researchers found significant associations between neuropathological biomarkers of AD, chronic vascular risk factors, and Qalb levels. They discovered that glucose exposure can directly or indirectly impact BBB integrity through Aβ and tau proteins, emphasizing the importance of glucose stability in managing and protecting against dementia. These findings shed light on the intricate connections between AD pathology, chronic vascular risk factors, and BBB dysfunction, providing new insights for potential therapeutic interventions. Dive deeper into this fascinating research by exploring the full article!

BackgroundBlood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer’s disease (AD) biomarkers and vascular factors are also associated with BBB permeability.ObjectiveIn the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated.MethodsThe cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors.ResultsThree types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aβ1-42 (B = −20.775, p = 0.009) and Aβ1-40 (B = −305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611–1.659, p < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662–1.694, p < 0.001).ConclusionGlucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.

Read Full Article (External Site)