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

DiFrancesco JC, Longoni M, Piazza F - Front Neurol (2015)

Bottom Line: Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease (AD).Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway.The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca , Monza , Italy ; The Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease βiomarkers (iCAβ) International Network , Monza , Italy.

ABSTRACT
Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease (AD). Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway. The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy. Herein, we critically review the growing body of evidence supporting the monitoring of CSF anti-Aβ autoantibody as a promising candidate biomarker for ARIA in clinical trials.

No MeSH data available.


Related in: MedlinePlus

Similarities between immunotherapy-induced ARIA and spontaneous ARIA-like events in CAA-ri. Upper row. Axial brain MRI revealing ARIA-E (A) and ARIA-H [(B), arrow] in one AD patient treated with bapineuzumab. Reproduced with permission from Ref. (3). Lower row. Axial brain MRI revealing spontaneous ARIA-E (C) and ARIA-H [(D), arrow] occurring in one CAA-ri patient from the “The inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers (iCAβ) International Network (20, 50).” Images (A,C) represent FLAIR-MRI sequences; (B,D) represent T2*-GRE sequences.
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Figure 1: Similarities between immunotherapy-induced ARIA and spontaneous ARIA-like events in CAA-ri. Upper row. Axial brain MRI revealing ARIA-E (A) and ARIA-H [(B), arrow] in one AD patient treated with bapineuzumab. Reproduced with permission from Ref. (3). Lower row. Axial brain MRI revealing spontaneous ARIA-E (C) and ARIA-H [(D), arrow] occurring in one CAA-ri patient from the “The inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers (iCAβ) International Network (20, 50).” Images (A,C) represent FLAIR-MRI sequences; (B,D) represent T2*-GRE sequences.

Mentions: Immunotherapy trials, in particular, have underlined the urgent need of safety biomarkers to avoid, or at least enable the early detection of the severe side effects of treatment termed amyloid-related imaging abnormalities (ARIA) (2). There are two types of ARIA: ARIA-E, characterized by the magnetic resonance imaging (MRI) evidence of vasogenic edema (VE) and/or sulcal effusion on fluid-attenuated inversion recovery (FLAIR), as hallmarks of inflammation at the level of the affected vessels; and ARIA-H, characterized by signal of hemosiderin deposits involving microhemorrhages (MHs) and superficial siderosis on T2*-weighted gradient echo (T2*-GRE) or susceptibility-weighted imaging (SWI), as hallmarks of cerebral amyloid angiopathy (CAA) (3) (Figures 1A,B).


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

DiFrancesco JC, Longoni M, Piazza F - Front Neurol (2015)

Similarities between immunotherapy-induced ARIA and spontaneous ARIA-like events in CAA-ri. Upper row. Axial brain MRI revealing ARIA-E (A) and ARIA-H [(B), arrow] in one AD patient treated with bapineuzumab. Reproduced with permission from Ref. (3). Lower row. Axial brain MRI revealing spontaneous ARIA-E (C) and ARIA-H [(D), arrow] occurring in one CAA-ri patient from the “The inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers (iCAβ) International Network (20, 50).” Images (A,C) represent FLAIR-MRI sequences; (B,D) represent T2*-GRE sequences.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4585101&req=5

Figure 1: Similarities between immunotherapy-induced ARIA and spontaneous ARIA-like events in CAA-ri. Upper row. Axial brain MRI revealing ARIA-E (A) and ARIA-H [(B), arrow] in one AD patient treated with bapineuzumab. Reproduced with permission from Ref. (3). Lower row. Axial brain MRI revealing spontaneous ARIA-E (C) and ARIA-H [(D), arrow] occurring in one CAA-ri patient from the “The inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers (iCAβ) International Network (20, 50).” Images (A,C) represent FLAIR-MRI sequences; (B,D) represent T2*-GRE sequences.
Mentions: Immunotherapy trials, in particular, have underlined the urgent need of safety biomarkers to avoid, or at least enable the early detection of the severe side effects of treatment termed amyloid-related imaging abnormalities (ARIA) (2). There are two types of ARIA: ARIA-E, characterized by the magnetic resonance imaging (MRI) evidence of vasogenic edema (VE) and/or sulcal effusion on fluid-attenuated inversion recovery (FLAIR), as hallmarks of inflammation at the level of the affected vessels; and ARIA-H, characterized by signal of hemosiderin deposits involving microhemorrhages (MHs) and superficial siderosis on T2*-weighted gradient echo (T2*-GRE) or susceptibility-weighted imaging (SWI), as hallmarks of cerebral amyloid angiopathy (CAA) (3) (Figures 1A,B).

Bottom Line: Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease (AD).Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway.The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca , Monza , Italy ; The Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease βiomarkers (iCAβ) International Network , Monza , Italy.

ABSTRACT
Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease (AD). Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway. The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy. Herein, we critically review the growing body of evidence supporting the monitoring of CSF anti-Aβ autoantibody as a promising candidate biomarker for ARIA in clinical trials.

No MeSH data available.


Related in: MedlinePlus