Fabrizio PiazzaUniversità degli Studi di Milano-Bicocca | UNIMIB · School of Medicine and Surgery
Fabrizio Piazza
Pharmaceutical Biotechnology, PhD in Molecular and Translational Medicine
Cerebral Amyloid Angiopathy and Alzheimer's disease Biomarkers and clinical trials
About
64
Publications
9,840
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1,305
Citations
Citations since 2017
Introduction
He is leading neurobiological researches applied to neurodegenerative and cerebrovascular diseases, with a focus on the immune-mediated mechanisms of the amyloid-related imaging abnormalities (ARIA) in CAA and in clinical trials for AD. From 2012, he is Coordinating the inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers International Network (iCAβ), a Global Consortium for the discovery of biomarkers of CAA and AD.
https://sites.google.com/site/icabinternationalnetwork
Additional affiliations
June 2017 - present
Italian National Research Council (CNR)
Position
- Research Associate
September 2015 - present
December 2010 - September 2015
Position
- Research Assistant
Description
- fabrizio.piazza@unimib.it
Publications
Publications (64)
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...
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...
At the 8th International Conference on Clinical Trials in Alzheimer's Disease held November 5-7, 2015 in Barcelona, Spain, promising data were presented on two candidate Alzheimer's disease immunotherapeutic agents, gantenerumab and aducanumab. Trial results demonstrated that the implementation of cerebrospinal fluid and Aβ-PET biomarkers improves...
Background and Objectives
To investigate the natural history and outcomes following treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri).
Methods
A multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic cr...
Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional...
Anemia is one of the most frequent diseases worldwide, affecting one-third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra-cerebral arterial and ven...
Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arteri...
Background and Objectives
Amyloid-related imaging abnormalities suggestive of vasogenic edema or sulcal effusion (ARIA-E) are the most common adverse events complicating Alzheimer’s disease (AD) immunotherapy with anti-amyloid-beta (Aβ) monoclonal antibodies (mAbs). ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflamma...
Background
Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report...
Introduction
Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) are commonly observed with anti-amyloid therapies in Alzheimer's disease. We developed a semi-mechanistic, in silico model to understand the time course of ARIA-E and its dose dependency.
Methods
Dynamic and statistical analyses of data from 112 individuals that experi...
https://n.neurology.org/content/author-response-spontaneous-aria-events-cerebral-amyloid-angiopathy%E2%80%93related-inflammation
Increased cerebrovascular amyloid-β (Aβ) deposition represents the main pathogenic mechanisms characterizing Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Whereas an increasing number of studies define the contribution of fibrin(ogen) to neurodegeneration, how other hemostasis factors might be pleiotropically involved in the AD an...
Amyloid related imaging abnormalities (ARIA) detected by magnetic resonance imaging (MRI) are associated with a class of therapeutic anti‐amyloid‐β antibodies under investigation in Alzheimer’s disease. ARIA‐E, manifested as bright signals on the T2 fluid attenuated inversion recovery (FLAIR) sequence, are suggestive of parenchymal vasogenic edema...
Two of the key functions of arteries in the brain are (1) the well‐recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional...
Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course a...
Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare and treatable variant of CAA likely due to an autoimmune response directed toward beta-amyloid deposits. Cognitive and behavioral manifestations are the most common symptoms, followed by focal neurological signs, headache and seizures, associated with characteristics neuroradiologi...
http://n.neurology.org/content/90/3/144.2
The superficial siderosis (SS) of the central nervous system (CNS) is a rare condition characterized by a wide range of neurological manifestations directly linked to an acquired iron-mediated neurodegeneration. First described more than 100 years ago, only recently SS has been divided into two distinct entities, according to the distribution of ir...
http://www.neurology.org/content/88/18/1768/reply#neurology_el%3B66123
Failure of the IV immunoglobulin trial highlighted a key issue in immunotherapy: identification of optimal drug dosing and timing in order to maximize efficacy while reducing the occurrence of amyloid-related imaging abnormalities (ARIA) side effects. [1]
A phase 1b study with...
Importance Cerebral amyloid angiopathy–related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy.
Objective To test the sensitivity...
We report a biomarker and genetic evaluation of four patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) treated with corticosteroids. Patients presented with focal symptomatology and cognitive impairment. MRI revealed cortical microbleeds and asymmetrical hyperintense white matter lesions (WML). Cerebrospinal fluid (CSF) biomar...
. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature.
Case Report
. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of el...
Background:
Cerebral amyloid angiopathy-related inflammation (CAA-ri) represents the most readily responsive form of CAA, if diagnosed and treated early. Although CAA-ri typically presents with a monophasic pattern, recurrences have been occasionally reported.
Objectives:
To describe the evolution of the clinical and neuroradiological features o...
Here is the preview of the iCAB International Network Website!!
Cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare form of vasculitis associated with amyloid-β (Aβ) deposition in vessel walls, has been proposed as a spontaneous human model of the amyloid-related imaging abnormalities (ARIA) occurring after anti-Aβ immunotherapy for the treatment of Alzheimer's disease (AD). We describe a case of...
The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from
55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological
diseases was determined using standardized commercially available kits for viral nucleic acid extraction...
The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction...
Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients...
Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients...
Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.
A possible hypothesis to explain depression sympt...
Beta-site APP-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals pr...
Anti-Aβ autoantibodies dosage in Cerebral Amyloid Angiopathy (CAA), CAA-related inflammation and Alzheimer’s disease for a better diagnosis and for a safe follow up and therapeutic purposes
http://assobiomedica.it/it/innovation-area/technology-transfer/anti-ass-autoantibodies-evaluation-in-alzheimer.html
Although the diverse triggers of AD are still under debate, the hypothesis of the contribution of cerebrovascular deficiencies has emerged in recent years. Cerebrovascular dysfunction may precede cognitive decline and onset of neurodegeneration. Indeed, the toxic Aβ(42) aggregates constituting senile plaques, one of AD hallmarks, is often detected...
We investigated the possible involvement of vascular damage in the pathogenesis of Alzheimer's disease (AD), by assessment of plasma levels of tissue factor pathway inhibitor (TFPI), a serine protease inhibitor induced by endothelial injury, and homocysteine (Hcy), a known risk factor for cerebrovascular disorders, folate levels were also measured....
Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers,...
The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation...
Acetyl-cholinesterase inhibitors (AChEI) are drugs frequently prescribed for the treatment of Alzheimer's disease (AD), exerting an effect on cognition, as well as on behavioural and psychological symptoms of dementia and activities of daily living. The efficacy of AChEI may be ascribed not only to the activation of cholinergic transmission, but al...
BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is a membrane-tethered member of the aspartyl proteases, essential for the production of beta-amyloid, a toxic peptide that accumulates in the brain of subjects affected by Alzheimer disease. The BACE1 C-terminal fragment contains a DXXLL motif that has been shown to bind the VHS (VPS27,...
Several lines of evidence implicate a central role for alpha-synuclein (aSN) in the pathogenesis of Parkinson's disease (PD). Besides rare genetic mutations, post-translational mechanisms, such as oxidative stress-related nitration, may alter the protein properties in terms of propensity to aggregate or be degraded. Our group previously described i...
Atherosclerosis is associated with Alzheimer's disease (AD) in humans, but the nature of this link is still elusive. Aim of this study was to investigate aortic atherosclerosis development in a mouse model with central nervous system (CNS) restricted beta-amyloid precursor protein (APP) overexpression.
APP23 mice, overexpressing the Swedish mutated...
To examine in vivo levels of BAFF (B-cell activating factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) in both the cerebrospinal fluid (CSF) and serum of 30 naïve MS patients and 79 subjects affected by acute or chronic inflammatory or non-inflammatory neurological diseases.
Case-control study.
No difference am...
In this brief paper we would like to hypothesize that platelets might represent a "peripheral" contributory source for the elevation of plasma glutamate levels in the setting of acute ischemic stroke: available evidence and possible mechanisms will be discussed, especially drawing attention to the possible relevance for the pathophysiology of early...
Down syndrome (DS) is the most common genetic disorder characterized by an extra copy of chromosome 21. DS subjects show signs of progressive cognitive decline, and most of them develop Alzheimer's type dementia at the age of 50 to 55 years. The aim of this study was to evaluate amyloid precursor protein (APP) metabolites and anti-Abeta 1-42 antibo...
Background: Statins have an established role in ischemic stroke prevention and
have been reported to be neuroprotective in experimental models of cerebral
ischemia, possibly via Akt signalling and increased production of nitric oxide.
We tested the effects of clinically meaningful doses of two chemically different
statins, simvastatin (hydrophobic...
Objective:
To identify the real number of hyperhomocysteinemic Alzheimer's patients who may benefit from homocysteine-lowering therapy.
Methods:
Basal and post-methionine load homocysteine levels were assessed by rp-HPLC system.
Results:
PML test revealed twice as many hyperhomocysteinemic AD subjects with respect to the fasting analysis.
Con...
Background: Inflammation and excitotoxicity play important roles in the pathophysiology
of ischemic brain damage. In previous studies we have shown a
prolonged TNF-alpha (TNF-a) release, a long lasting high glutamate (glu) plasma
concentration and an impaired platelet (plt) glu transport up to 3 months after
the symptoms onset. Since high persistin...
Questions
Question (1)
Dear CAA Community,
The Journal of Alzheimer's disease (JAD) is one of the top 10 most productive journals publishing CAA-related research. (ref JNNP 2015).
As an Associate Editor for JAD, I warmly recommend you to consider JAD for your next manuscript submissions.
If you would like to select me as the Serving Editor for your submission, please remember to suggest my name (Dr Piazza Fabrizio) as Handling Associate Editor on the Cover Letter, I will be honoured to handle your manuscript!
Projects
Projects (3)
To collaborate with iCAB Network in the study of the CAA-ri
Leading clinico-therapeutic recommendations and trial’s safety biomarkers to guide immunotherapy trials of Cerebral Amyloid Angiopathy and Alzheimer’s disease is the main goal of the the biomarkARIA Research Project and iCAB International Network, the largest global effort aimed at deciphering the pathogenetic mechanisms of ARIA, with more than 35 centers involved.
Dr Piazza Fabrizio is leading neurobiological and translational researches applied to neurodegenerative, neuroimmunological and cerebrovascular disorders, with a particular focus on the immune-mediated mechanisms and the amyloid-related imaging abnormalities (ARIA) in the pathogenesis of Cerebral Amyloid Angiopathy-related inflammation and during the Amyloid beta disease modifying treatments for Alzheimer’s disease.
Dr Piazza is the founding Member and Coordinator of the inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease βiomarkers International Network (iCAβ), a World-Wide rent involvinig 35 leading Centers of Excellence on AD and CAA from 12 different Countries, established in 2012
The validation of diagnostic, prognostic and safety biomarkers of ARIA, as well as the definition of clinico-therapeutic recommendations to guide CAA and AD immunotherapy trials, is the main goal of the the biomarkARIA Research Project and iCAB International Network, the largest worldwide effort aimed at deciphering the pathogenetic mechanisms of ARIA in a translational and cooperatively-open design between academia and pharma companies.
WebSite URL:
https://sites.google.com/site/icabinternationalnetwork
