CSF and Plasma Biomarkers in Patients With Iatrogenic Cerebral Amyloid Angiopathy.

Neurology

From the Cerebrovascular Unit (G.P., A.P., G.G., T.C., G.M., C.T., I.C., N.R., G.B.B., A.B., L.G., B.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Pharmacological and Biomolecular Sciences (G.P., A.P.), University of Milan; Department of Neurology (J.C.D., P.T.D.), Fondazione IRCCS San Gerardo dei Tintori, Monza; Neuroradiology Unit (M.S., A.E.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; ALS Centre (M.S.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin; Neuropathology Unit (P.C., G.D.F., M.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; and Istituti Clinici Scientifici Maugeri IRCCS (A.Z., E.A.P.), Neurorehabilitation Unit of Milan Institute, Italy.

Published: October 2024

AI Article Synopsis

  • A new subset of cerebral amyloid angiopathy (CAA) patients, termed iatrogenic CAA (iCAA), is characterized by early onset and is believed to be caused by medical factors, differing from sporadic CAA (sCAA).
  • The study involved analyzing cerebrospinal fluid (CSF) and plasma levels of β-Amyloid and tau proteins in patients diagnosed with either iCAA or sCAA in a clinical setting across two research centers.
  • Results indicated that patients with sCAA had more cognitive impairments and cardiovascular risks compared to iCAA patients, but levels of key biomarkers (Aβ40, Aβ42, total tau) in both CSF and plasma were similar between the two groups.

Article Abstract

Objectives: Recently, a subset of patients affected by cerebral amyloid angiopathy (CAA) distinguished by atypical juvenile onset and a hypothesized iatrogenic origin (iatrogenic CAA, iCAA) has emerged. β-Amyloid (Aβ) accumulation evidenced by amyloid PET positivity or CSF Aβ decrease was included in the iCAA diagnostic criteria. Conversely, diagnostic criteria for sporadic CAA (sCAA) do not involve biomarker analysis. The aim of this study was to assess CSF and plasma levels of Aβ and tau in iCAA and sCAA cohorts.

Methods: Patients affected by probable or possible CAA according to established criteria (Boston 2.0) were prospectively recruited at Fondazione IRCCS Carlo Besta and San Gerardo dei Tintori from May 2021 to January 2024. Patients with probable and possible iCAA or sCAA with available plasma and/or CSF samples were included. Clinical and neurologic data were collected, and levels of Aβ40, Aβ42, total tau, and phospho-tau (p-tau) were assessed in CSF and plasma by SiMoA and Lumipulse.

Results: 21 patients with iCAA (72% male, mean age at symptom onset 50 years [36-74]) and 32 patients with sCAA (44% male, mean age at symptom onset 68 years [52-80]) were identified. Cognitive impairment and cardiovascular risk factors in the sCAA cohort were more common compared with the iCAA cohort. Patients with sCAA and iCAA showed similar CSF levels for Aβ40 ( = 0.5 [sCAA, 95% CI 2,604-4,228; iCAA, 95% CI 1,958-3,736]), Aβ42 ( = 0.7 [sCAA, 95% CI 88-157; iCAA, 95% CI 83-155]), and total tau ( = 0.08 [sCAA, 95% CI 80-134; iCAA, 95% CI 37-99]). Plasma levels of Aβ40 ( = 0.08, 95% CI 181-222), Aβ42 ( = 0.3, 95% CI 6-8), and total tau ( = 0.4, 95% CI 3-6) were not statistically different in patients with sCAA compared with iCAA ones (Aβ40, 95% CI 153-193; Aβ42, 95% CI 6-7 and total tau, 95% CI 2-4).

Discussion: Despite presenting with a younger age at onset, fewer cardiovascular risk factors, and lower cognitive impairment, patients with iCAA demonstrated Aβ and tau levels comparable with elderly patients with sCAA, supporting a common molecular paradigm between the 2 CAA forms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399065PMC
http://dx.doi.org/10.1212/WNL.0000000000209828DOI Listing

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