Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation

Abstract

We studied longitudinal changes of the levels of anti-amyloid β (anti-Aβ) antibody, amyloid β (Aβ) protein, and interleukin 8 (IL-8) in cerebrospinal fluid (CSF) of a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) in whom steroid treatment resulted in clinical improvement. The diagnosis of CAA-ri was established with brain biopsy. Levels of anti-Aβ 42 antibody, Aβ 40, Aβ 42 and IL-8 in CSF were measured in the CAA-ri patient at 23 time points in the 8-month clinical course. These CSF samples were divided into 2 groups: those obtained before (n = 12) and those after (n = 11) oral corticosteroid therapy was started. We compared these levels between CSF samples obtained before and after therapy. The mean levels of anti-Aβ 42 antibody and IL-8 were significantly higher in CSF samples of the CAA-ri patient before oral corticosteroid therapy than those after therapy. A positive correlation was noted between levels of anti-Aβ 42 antibodies and IL-8 in CSF of this patient. There were no significant differences of mean levels of Aβ 40 and Aβ 42 between CSF samples obtained before and after oral corticosteroid therapy. It was possible that the autoinflammatory process with anti-Aβ 42 antibodies and IL-8 may have been involved in the pathogenesis of CAA-ri, and that corticosteroid therapy directly affected levels of anti-Aβ 42 antibody and IL-8. In summary, CAA-ri encephalopathy is a relapsing or progressive disorder and may be treatable by adequate immunosuppressive therapy. The anti-Aβ 42 antibody in CSF is a useful biological marker for therapeutic monitoring of CAA-ri.

Anti-Aβ Autoantibodies in Amyloid Related Imaging Abnormalities (ARIA): Candidate Biomarker for Immunotherapy in Alzheimer’s Disease and Cerebral Amyloid Angiopathy

“…However, considering the less invasive procedure compared to CSF, further investigations in a larger population will be of certain interest. Second, the temporal relationship between anti-Aβ autoantibody levels and clinical and radiological improvement of CAA-ri strongly supports they are a specific trait of the VE and MHs processes (ARIA-like events) ( 13 , 16 , 21 , 46 ). Third, like in AD-treated patients, the increased CSF level of Aβ40 and Aβ42, the decreased amyloid-PET uptake, and the higher amounts of anti-Aβ autoantibodies indicate a transient massive drainage of Aβ from the brain and vascular deposits to its soluble forms ( 18 , 20 , 31 , 47 ).…”

“…First, like in immunotherapy, the acute phase of CAA-ri is characterized by a specific immune reaction mediated by an increased amount of autologous CSF antibodies against the perivascular deposited Aβ typical of CAA ( 13 , 16 , 21 , 44 – 46 ). Although observed in a single case study, autoantibodies have been found to be intrathecally produced and specifically increased only in CSF, while no changes has been found in the plasma, thus reflecting the immune/inflammatory mechanisms restricted to the brain ( 13 ).…”

Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome

“…The search (Figure 2) identified 186 abstracts, and a further 44 from reference lists, giving a total of 230. After inclusion and exclusion criteria were applied, 104 publications were included which described 213 distinct pathologically proven cases of CAARI/ABRA, 4,7…”

Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy‐related inflammation

“…8,9 Also, anti-Aβ antibodies and factors, in relation to inflammation and tissue damage, could be implicated in the initiation and progression of CAA-ri. 10 More convenient biomarkers related to CAA-ri, however, are required to begin treatments as soon as possible.…”