Characterizing mixed location hemorrhages/microbleeds with CSF markers

Ulf Jensen-Kondering, Nils G. Margraf*, Caroline Weiler, Walter Maetzler, Justina Dargvainiene, Kim Falk, Sarah Philippen, Thorsten Bartsch, Charlotte Flüh, Christoph Röcken, Bettina Möller, Georg Royl, Alexander Neumann, Norbert Brüggemann, Benjamin Roeben, Claudia Schulte, Benjamin Bender, Daniela Berg, Gregor Kuhlenbäumer

*Corresponding author for this work
1 Citation (Scopus)


Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer’s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. 

Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. 

Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Original languageEnglish
JournalInternational Journal of Stroke
Issue number6
Pages (from-to)728-735
Number of pages8
Publication statusPublished - 07.2023

Research Areas and Centers

  • Academic Focus: Biomedical Engineering

DFG Research Classification Scheme

  • 205-32 Medical Physics, Biomedical Engineering
  • 206-05 Experimental Models for Investigating Diseases of the Nervous System

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