Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

Abstract

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA–ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Aquaporin-4 cerebrospinal fluid levels are higher in neurodegenerative dementia: looking at glymphatic system dysregulation

“…It is interesting to point out that the same lack of correlation was found in the Bergström et al study [ 22 ]. The relationship between AQP4 and Aβ was analysed in a study published in March 2021 [ 30 ], which focused on the circulating levels of AQP4 and the cerebral amyloid angiopathy-associated intracerebral haemorrhage (CAA-ICH). Despite being not able to demonstrate any significant difference between CAA-ICH patients and controls, this study showed a very interesting association between serum AQP4 levels and the load of cerebral haemorrhages in the CAA cohort; AQP4 levels were lower in the serum of patients suffering cognitive impairment, implying a very important link between Aβ clearance and AQP4 expression.…”

Aquaporin-4 and Cognitive Disorders

“…A recent study analyzed AQP4 expression in the circulation of CAA patients with intracerebral hemorrhage and demonstrated that lower circulating levels of AQP4 were related to ApoE ε4 carriers, cognitive impairment and previous hemorrhagic stroke. However, the AQP4 level did not remain independently associated with cognitive impairment in the binary logistic regression analysis [ 63 ]. The relationship between Aβ and tau deposition and PSD has attracted attention, but there is still a lack of convincing evidence [ 64 ].…”

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy

“…The population studied in this cohort consisted of 126 participants who had suffered at least one lobar ICH and presented a clinical suspicion of CAA. Patients were recruited during a follow-up visit in 11 different Spanish centers ( Bonaterra-Pastra et al, 2021 ; Marazuela et al, 2021 ). All patients were >55 years old and those presenting with symptomatic deep ICHs or treated with anticoagulant therapy were excluded.…”