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Background: Blood-brain barrier (BBB) dysfunction could favor the pathogenesis and progression of Alzheimer's disease (AD). Vascular risk factors (VRF) could worsen BBB integrity, thus promoting neurode generation. Objective: To investigate BBB permeability and its relation with VRF along the AD continuum (ADc). Cerebrospinal fluid (CSF) Amyloid (A) and p-tau (T) levels were used to stratify patients. Methods: We compared CSF/plasma albumin ratio (QAlb) of 131 AD patients and 24 healthy controls (HC). APOE genotype and VRF were evaluated for each patient. Spearman's Rho correlation was used to investigate the associations between Qalb and CSF AD biomarkers. Multivariate regression analyses were conducted to explore the relationship between Qalb and AD biomarkers, sex, age, cognitive status, and VRF. Results: QAlb levels did not show significant difference between ADc patients and HC (p = 0.984). However, QAlb was significantly higher in A + T–compared to A + T+ (p = 0.021). In ADc, CSF p-tau demonstrated an inverse correlation with QAlb, a finding confirmed in APOE4 carriers (p = 0.002), but not in APOE3. Furthermore, in APOE4 carriers, sex, hypertension, and hypercholesterolemia were associated with QAlb (p = 0.004, p = 0.038, p = 0.038, respectively), whereas only sex showed an association in APOE3 carriers (p = 0.026). Conclusions: BBB integrity is preserved in ADc. Among AT categories, A + T–have a more permeable BBB than A + T+. In APOE4 carriers, CSF p-tau levels display an inverse association with BBB permeability, which in turn, seems to be affected by VRF. These data suggest a possible relationship between BBB efficiency, VRF and CSF p-tau levels depending on APOE genotype. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation is an important player in Alzheimer's disease (AD), whose effects can be influenced by the blood–brain barrier (BBB). Here, we investigated the relationship between BBB permeability, indicated by cerebrospinal fluid (CSF)/plasma albumin quotient (Qalb), and CSF indexes of neuroinflammation in a cohort of biologically defined AD patients. Methods: Fifty‐nine consecutive patients with mild cognitive impairment (MCI) or early AD (Mini‐Mental State Examination [MMSE] >22) underwent CSF analysis for inflammatory cytokines (interleukin [IL]‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, Il‐10, IL‐12, IL‐13, IL‐17, tumor necrosis factor‐α [TNF‐α], interferon‐γ [IFN‐γ], granulocyte‐monocyte colony‐stimulating factor [GM‐CSF], granulocyte colony‐stimulating factor [G‐CSF]). Using backward stepwise linear regression analysis, we explored the potential influence of each cytokine CSF level on Qalb considering age, sex, and apolipoprotein E (APOE) as covariates. Results: Higher levels of IL‐4 (β = 0.356, 0.005) and IL‐8 (β = 0.249, 0.05) were associated with higher Qalb values, while macrophage inflammatory protein‐1α (MIP‐1β) (β = −0.274; p = 0.032) and TNF‐α (β = −0.248; p = 0.031) showed a significant negative association with BBB permeability. Age was also positively associated with Qalb (β = 0.283; p = 0.016). Conclusions: Despite the overall integrity of the BBB, its permeability could either influence or be influenced by central neuroinflammation, reflected by CSF cytokine levels. This is in line with previous studies that showed that patients with a more intact barrier are those with more prominent neurodegeneration. Our findings suggest that different neuroinflammatory profiles can be associated with different levels of BBB permeability in AD. [ABSTRACT FROM AUTHOR]

Background and Purpose: The locus coeruleus (LC) provides dopamine/noradrenaline (DA/NA) innervation throughout the brain and undergoes early degeneration in Alzheimer's disease (AD). We evaluated catecholaminergic enzyme levels in the cerebrospinal fluid (CSF) of a group of patients biologically defined as within the AD continuum (ADc) and explored their relationship with AD biomarkers and cytokine/growth factor levels to investigate their interplay with neurodegenerative and neuroinflammatory processes. Methods: The CSF concentration of DA transporter (DAT), tyrosine‐hydroxylase (TH), DOPA‐decarboxylase (DDC), and dopamine‐β‐hydroxylase (DβH), as well as cytokine/growth factor levels, were analyzed in 41 ADc patients stratified according to CSF beta‐amyloid (Aβ)1‐42 (A) and p‐tau (T) in AD pathological changes (A+ T‐) and AD (A+ T+) subgroups, as well as in 15 control subjects (A‐ T‐). Results: The ADc group had lower CSF levels of DAT and TH but increased DβH levels to compensate for NA synthesis. DDC levels were higher in the A+ T+ subgroup but comparable with controls in the A+ T– subgroup, probably because the DA system is resilient to the degeneration of LC neurons in the absence of tau pathology. Adjusting for age, sex, APOE genotype, and cognitive status, a significant association was found between TH and Aβ1‐42 (R2 = 0.25) and between DDC and p‐tau (R2 = 0.33). Finally, TH correlated with interleukin (IL)‐10 levels (p = 0.0008) and DβH with IL‐1β (p = 0.03), IL‐4 (p = 0.02), granulocyte colony‐stimulating factor (p = 0.007), and IL‐17 (p = 0.01). Conclusions: Taken together, these findings suggest that catecholaminergic enzymes, functional markers of the catecholaminergic system, are closely linked to the neurodegenerative and neuroinflammatory processes in AD pathology. [ABSTRACT FROM AUTHOR]

Biobanking has emerged as a strategic challenge to promote knowledge on neurological diseases, by the application of translational research. Due to the inaccessibility of the central nervous system, the advent of biobanks, as structure collecting biospecimens and associated data, are essential to turn experimental results into clinical practice. Findings from basic research, omics sciences, and in silico studies, definitely require validation in clinically well-defined cohorts of patients, even more valuable when longitudinal, or including preclinical and asymptomatic individuals. Finally, collecting biological samples requires a great effort to guarantee respect for transparency and protection of sensitive data of patients and donors. Since the European General Data Protection Regulation 2016/679 has been approved, concerns about the use of data in biomedical research have emerged. In this narrative review, we focus on the essential role of biobanking for translational research on neurodegenerative diseases. Moreover, we address considerations for biological samples and data collection, the importance of standardization in the preanalytical phase, data protection (ethical and legal) and the role of donors in improving research in this field. [ABSTRACT FROM AUTHOR]

Glial and microglial cells contribute to brain glucose consumption and could actively participate in shaping patterns of brain hypometabolism. Here, we aimed to investigate the association between 18F-fluorodeoxyglucose (18F-FDG) uptake and markers of microglial and astrocytic activity in a cohort of patients with Alzheimer's Disease (AD). We dosed cerebrospinal fluid (CSF) levels of soluble Triggering Receptor Expressed on Myeloid cells (sTREM2), Glial Fibrillary Acidic Protein (GFAP), a marker of reactive astrogliosis, and β-S100, a calcium-binding protein associated with a neurotoxic astrocytic profile. No associations were found between sTREM-2 and 18F-FDG uptake. Instead, 18F-FDG uptake was associated negatively with CSF β-S100 in the left supramarginal gyrus, inferior parietal lobe and middle temporal gyrus (Brodmann Areas (BA) 21 and 40). Increased β-S100 levels could negatively regulate neuronal activity in the temporo-parietal cortex to prevent damage associated with AD hyperactivity, or rather they could reflect neurotoxic astrocytic activation contributing to AD progression in key strategic areas. We also identified a trend of positive association of 18F-FDG uptake with CSF GFAP in the right fronto-medial and precentral gyri (BA 6, 9 and 11), which has been reported in early AD and could either be persisting as an epiphenomenon tied to disease progression or be specifically aimed at preserving functions in the frontal cortex. Overall, CSF markers of astrogliosis seem to correlate with cortical glucose uptake in symptomatic sporadic AD, highlighting the role of astrocytes in shaping regional hypometabolism and possibly clinical presentation. [ABSTRACT FROM AUTHOR]