Correlation of blood–brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease

Abstract

BackgroundBlood–brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD.MethodsA total of 139 individuals were divided into probable AD (18F-florbetapir PET positive, n = 101) and control group (cognitively normal, n = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aβ40, Aβ42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging.ResultsPatients with AD had higher Qalb (p = 0.0024), higher numbers of CMBs (p = 0.03), and greater CSVD burden (p < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb (p = 0.03), and the numbers of CMBs negatively correlated with CSF Aβ42 (p = 0.02).ConclusionBlood–brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.

Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction-Disruption with an Increased Risk of Hemorrhagic and Ischemic Stroke That Is Capable of Exacerbating Neurodegeneration

“…[17]. This group believes strongly that BBBdd is responsible for CMBs as put forth earlier in the text along with multiple other authors [18][19][20][21]. Risk factors for the development of CMBs consist of advancing age, HTN, CAA, type 2 diabetes mellitus (T2DM), smoking, and previous strokes [1,3,17].…”

“…[17]. Indeed, BBBdd allows for increased permeability and this could lead to the extravasation of RBCs from cerebral microvessels into the neuropil interstitial space, which leads to the deterioration of the brain's environment and further aggrevate brain degeneration due to the development of CMBs [17][18][19][20][21]38]. Additionally, the next or concurrent steps in the progression to CMBs would be one of two primary etiologies or mechanisms HTN or CAA to develop CMBs.…”

“…Additionally, the plasma that is extruded from these microbleeds contains neurotoxic thrombin, plasmin, and the components within the complement cascade [1,15,16]. The information regarding the possibility of the BECact/dys and subsequent or concurrent NVU BBBdd is currently gaining a great deal of support [17][18][19][20][21].…”

Mesoporous Silica Nanoparticles: Types, Synthesis, Role in the Treatment of Alzheimer’s Disease, and Other Applications

“…In AD, disrupted mitochondrial function leads to compromised energy generation and an augmented susceptibility to oxidative stress. These factors synergistically advance neuronal degeneration [ 24 , 25 ].…”

Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms

“…Similarly, it has been suggested that small vessel disease may have some relationship with BBB dysfunction [ 47 , 48 ]. In the current literature, it is uncertain whether small vessel disease causes BBB damage or whether BBB disruption leads to small vessel disease.…”