Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Carmona Iraguiemail, M., Fernández Arcos, A., Alcolea, D., Piazza, F., Morenas Rodriguez, E., Antón Aguirre, S., et al. (2014). Biomarkers in cerebral amyloid angiopathy-related inflammation. Intervento presentato a: Alzheimer's Association International Conference (AAIC), Copenhagen, Denmark [10.1016/j.jalz.2014.05.807].
Biomarkers in cerebral amyloid angiopathy-related inflammation
PIAZZA, FABRIZIO;
2014
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.