Biomarkers in cerebral amyloid angiopathy-related inflammation

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare meningoencephalitis that presents with focal neurological deficits, cortical microbleeds and asymmetrical white matter lesions, usually steroid-responsive. It shares radiological features with amyloid related imaging abnormalities (ARIA), described in Alzheimer's disease (AD) patients that receive antiamyloid therapies, suggesting a common pathophysiological process. Clinical, neuropsychological and radiological description; APOE genotyping and cerebrospinal fluid (CSF) biomarkers (Aβ 42, Aβ 40, t-Tau, p-Tau and anti-A b autoantibodies) were determined in four patients with probable CAA-ri. PET imaging with Florbetapir was performed in two subjects, and one of them had a PET-PIB additionally. Patients received steroids and were clinically evaluated. T hree patients had imaging and CSF follow-up. Mean age of presentation was 73.5 years (range 69-78), 50% were men. All patients presented with neurological focal symptoms and cognitive impairment. MRI showed cortical microbleeds and asymmetrical hyperintense white matter lesions. Allelic frequency for APOE-e4 was 62.5%. Aß40 and Aß42 levels were decreased and anti-Ab autoantibodies were high in all cases. A PET with Florbetapir, performed in two patients, and a PET-PIB performed in one of them, showed cortical amyloid deposits. After corticosteroid administration, a complete (1/4) or partial (3/4) resolution of focal symptoms was observed. One patient suffered an intracerebral lobar hemorrhage six months after the resolution of focal symptoms. On the follow-up MRI, a significant reduction of white matter lesions was appreciated. CSF anti-Ab autoantibodies at follow-up were markedly reduced in all cases. The pattern in CSF and amyloid PET biomarkers and the presence of APOE-e4 in CAA-ri suggests an important role of vascular amyloidosis. Anti-Ab autoantibodies may be a specific biomarker for this process, and could be useful for CAA-ri diagnosis and monitoring the response to treatment.