Abstract
Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.
| Original language | English |
|---|---|
| Pages (from-to) | 449-458 |
| Number of pages | 10 |
| Journal | Annals of Neurology |
| Volume | 73 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2013 |
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ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation : Implications for amyloid-modifying therapies. / Piazza, Fabrizio; Greenberg, Steven M.; Savoiardo, Mario; Gardinetti, Margherita; Chiapparini, Luisa; Raicher, Irina; Nitrini, Ricardo; Sakaguchi, Hideya; Brioschi, Monica; Billo, Giuseppe; Colombo, Antonio; Lanzani, Francesca; Piscosquito, Giuseppe; Carriero, Maria Rita; Giaccone, Giorgio; Tagliavini, Fabrizio; Ferrarese, Carlo; Difrancesco, Jacopo C.
In: Annals of Neurology, Vol. 73, No. 4, 04.2013, p. 449-458.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation
T2 - Implications for amyloid-modifying therapies
AU - Piazza, Fabrizio
AU - Greenberg, Steven M.
AU - Savoiardo, Mario
AU - Gardinetti, Margherita
AU - Chiapparini, Luisa
AU - Raicher, Irina
AU - Nitrini, Ricardo
AU - Sakaguchi, Hideya
AU - Brioschi, Monica
AU - Billo, Giuseppe
AU - Colombo, Antonio
AU - Lanzani, Francesca
AU - Piscosquito, Giuseppe
AU - Carriero, Maria Rita
AU - Giaccone, Giorgio
AU - Tagliavini, Fabrizio
AU - Ferrarese, Carlo
AU - Difrancesco, Jacopo C.
PY - 2013/4
Y1 - 2013/4
N2 - Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.
AB - Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.
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UR - http://www.scopus.com/inward/citedby.url?scp=84878407495&partnerID=8YFLogxK
U2 - 10.1002/ana.23857
DO - 10.1002/ana.23857
M3 - Article
C2 - 23625526
AN - SCOPUS:84878407495
VL - 73
SP - 449
EP - 458
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 4
ER -