Enpowering Progression Risk of Cerebral Amyloid Angiopathy

NCT06960538 | Completed

• 1 other identifier: PRIORITY
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral amyloid angiopathy (CAA) is a microangiopathy characterized by the progressive deposition of β-amyloid in cerebral vessel walls, contributing to intracerebral hemorrhages, cognitive decline, and other clinical manifestations. Despite recent advances in diagnosis and understanding, many pathogenic, prognostic, and therapeutic aspects remain unclear. Study Objective: PRIORITY is a prospective observational study aimed at identifying clinical, neuroradiological, and biochemical biomarkers that could improve early diagnosis, risk stratification, and the identification of personalized therapeutic targets for CAA.

Conditions

Cerebral Amyloid Angiopathy; CAA - Cerebral Amyloid Angiopathy

Keywords

Cerebral Amyloid Angiopathy; CAA; plasma biomarkers; cerebrospinal fluid biomarkers

Outcome Measures

Primary Outcomes (3)

• Clinical Progression of CAA

  Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through clinical assessments. At baseline, clinical data (e.g., history of stroke, a diagnosis of dementia, presence of seizures, gait disturbances, vascular risk factors, prior brain injury/surgery, family history, medications…) recorded in a binary (yes/no) scale, indicating the presence or absence of each condition or risk factor, will be collected for each patient. During follow-up, new clinical events (e.g., number of new ICH-intracerebral hemorrhages, number of new ischemic stroke, presence of seizures, presence of TFNEs, cognitive status, death) will be recorded and compared with T0.

  Baseline (T0), 12 months (T1), 24 months (T2).

• Radiological Progression of CAA

  Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through neuroimaging markers (MRI). MRI assessment at baseline will include T1, T2, FLAIR, T2\*, GRE, SWI, and DWI sequences. Imaging will be assessed using STRIVE (Standards for Reporting Vascular Changes on Neuroimaging) criteria, with standardized rating scales for: number of Microbleeds (Microbleed Anatomical Rating Scale - MARS); presence of Lobar ICH- intracerebral hemorrhages; presence of Superficial siderosis; presence of White matter lesions (Fazekas scale: o to 3 scores, where 0 means absence of white matter lesions and 3 large presence of them); presence of Perivascular spaces (CSO-PVS); presence of Cortical microinfarcts; presence of Global cortical atrophy; presence of Subarachnoid haemorrhage. Follow-up includes repeated MRI with the same sequences. MRI changes will be evaluated with the same standardized rating scales for progression or appearance of the same parameters evaluated in T0.

  Baseline (T0), 12 months (T1), 24 months (T2).

• Identification of Protein and Lipid Biomarkers

  Analysis of cerebrospinal fluid and plasma to identify protein (e.g., concentrations in pg/mL of total Tau, p-Tau, Aβ42/Aβ40, NfL, GFAP) and lipid (qTOF-MS) signatures associated with CAA progression.

  Baseline (T0), 12 months (T1), 24 months (T2).

Secondary Outcomes (5)

• Cognitive Decline Assessment

  Baseline (T0), 12 months (T1), 24 months (T2).

• Development of a Predictive Model for Disease Progression

  24 months (T2).

• Hemorrhagic and Non-Hemorrhagic Event Incidence

  24 months (T2)

• Therapeutic Target Identification

  24 months (T2)

• Functional assessment

  Baseline (T0), 12 months (T1), 24 months (T2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with possible or probable CAA identified on brain MRI according to modified Boston Neuroradiological Criteria 2.0 regardless of age.

You may qualify if:

• patients of either sex over 18 years of age;
• patients with possible and probable symptomatic or asymptomatic CAA with or without histological demonstration (modified Boston criteria);
• patients who have had at least one brain MRI.

You may not qualify if:

• patients who have contraindications to undergoing brain MRI (e.g., pacemaker, incompatible mechanical valves, claustrophobia);
• patients who have contraindications to or refuse to undergo lumbar puncture;
• patients who are unable to provide informed consent for the study due to aphasic or cognitive impairment;
• patients who are pregnant or breastfeeding.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (1)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

Location

Related Publications (8)

• Pollaci G, Potenza A, Gorla G, Carrozzini T, Marinoni G, De Toma C, Canavero I, Rifino N, Boncoraglio GB, Difrancesco JC, Damavandi PT, Stanziano M, Erbetta A, Caroppo P, Di Fede G, Catania M, Zulueta A, Parati EA, Bersano A, Gatti L, Storti B. CSF and Plasma Biomarkers in Patients With Iatrogenic Cerebral Amyloid Angiopathy. Neurology. 2024 Oct 22;103(8):e209828. doi: 10.1212/WNL.0000000000209828. Epub 2024 Sep 16.

  PMID: 39284112 BACKGROUND

• Cheng X, Su Y, Wang Q, Gao F, Ye X, Wang Y, Xia Y, Fu J, Shen Y, Al-Shahi Salman R, Dong Q. Neurofilament light chain predicts risk of recurrence in cerebral amyloid angiopathy-related intracerebral hemorrhage. Aging (Albany NY). 2020 Nov 18;12(23):23727-23738. doi: 10.18632/aging.103927. Epub 2020 Nov 18.

  PMID: 33221749 BACKGROUND

• Wang SY, Chen W, Xu W, Li JQ, Hou XH, Ou YN, Yu JT, Tan L. Neurofilament Light Chain in Cerebrospinal Fluid and Blood as a Biomarker for Neurodegenerative Diseases: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2019;72(4):1353-1361. doi: 10.3233/JAD-190615.

  PMID: 31744001 BACKGROUND

• Palmqvist S, Janelidze S, Stomrud E, Zetterberg H, Karl J, Zink K, Bittner T, Mattsson N, Eichenlaub U, Blennow K, Hansson O. Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease-Related beta-Amyloid Status. JAMA Neurol. 2019 Sep 1;76(9):1060-1069. doi: 10.1001/jamaneurol.2019.1632.

  PMID: 31233127 BACKGROUND

• Gatti L, Tinelli F, Scelzo E, Arioli F, Di Fede G, Obici L, Pantoni L, Giaccone G, Caroppo P, Parati EA, Bersano A. Understanding the Pathophysiology of Cerebral Amyloid Angiopathy. Int J Mol Sci. 2020 May 13;21(10):3435. doi: 10.3390/ijms21103435.

  PMID: 32414028 BACKGROUND

• Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways. Nat Rev Neurol. 2020 Jan;16(1):30-42. doi: 10.1038/s41582-019-0281-2. Epub 2019 Dec 11.

  PMID: 31827267 BACKGROUND

• Banerjee G, Ambler G, Keshavan A, Paterson RW, Foiani MS, Toombs J, Heslegrave A, Dickson JC, Fraioli F, Groves AM, Lunn MP, Fox NC, Zetterberg H, Schott JM, Werring DJ. Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy. J Alzheimers Dis. 2020;74(4):1189-1201. doi: 10.3233/JAD-191254.

  PMID: 32176643 BACKGROUND

• Charidimou A, Boulouis G, Frosch MP, Baron JC, Pasi M, Albucher JF, Banerjee G, Barbato C, Bonneville F, Brandner S, Calviere L, Caparros F, Casolla B, Cordonnier C, Delisle MB, Deramecourt V, Dichgans M, Gokcal E, Herms J, Hernandez-Guillamon M, Jager HR, Jaunmuktane Z, Linn J, Martinez-Ramirez S, Martinez-Saez E, Mawrin C, Montaner J, Moulin S, Olivot JM, Piazza F, Puy L, Raposo N, Rodrigues MA, Roeber S, Romero JR, Samarasekera N, Schneider JA, Schreiber S, Schreiber F, Schwall C, Smith C, Szalardy L, Varlet P, Viguier A, Wardlaw JM, Warren A, Wollenweber FA, Zedde M, van Buchem MA, Gurol ME, Viswanathan A, Al-Shahi Salman R, Smith EE, Werring DJ, Greenberg SM. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study. Lancet Neurol. 2022 Aug;21(8):714-725. doi: 10.1016/S1474-4422(22)00208-3.

  PMID: 35841910 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Each patient will undergo CSF collection at baseline (T0) and blood sampling at T0, T1, and T2. CSF is collected via lumbar puncture, processed according to international guidelines, centrifuged, aliquoted, and stored at -80 °C. Blood plasma is isolated using Ficoll gradient centrifugation and similarly stored. CSF biomarkers (Aβ42, Aβ40, t-Tau, p-Tau) are measured via LUMIPULSE G assays (Fujirebio); plasma markers (Aβ42, Aβ40, t-Tau, NfL, GFAP) via ELISA or SIMOA (Quanterix). Untargeted lipidomic profiling (qTOF) of CSF and plasma includes sterols, glycerolipids, phospholipids, sphingolipids, fatty acids, and ether lipids. All patients undergo apoE genotyping; those with family history of CAA, ICH, or cognitive decline are screened for APP, TTR, and PSEN1 variants.

MeSH Terms

Conditions

Cerebral Amyloid Angiopathy; Cerebral Amyloid Angiopathy, Familial

Condition Hierarchy (Ancestors)

Cerebral Arterial Diseases; Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Cerebral Small Vessel Diseases; Amyloidosis, Familial; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: May 7, 2025
• Study Start: November 1, 2021
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)