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Published on: December 28, 2014
Characterizing mixed location hemorrhages/microbleeds with CSF markers
Ulf Jensen-Kondering1,2, Nils G Margraf3, Caroline Weiler3
1Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Kiel, Germany.
Insights
Mixed location hemorrhages (MLH) and cerebral amyloid angiopathy (CAA) may co-occur, suggesting they are part of a disease spectrum. This research clarifies their relationship in elderly patients with brain hemorrhages.
Area of Science:
- Neurology
- Neuroscience
- Geriatrics
Background:
- Cerebral amyloid angiopathy (CAA) causes lobar hemorrhages in the elderly, diagnosed by lobar lesions or cortical superficial siderosis (cSS).
- Hypertensive arteriopathy (HTN-A) causes deep hemorrhages; its presence with lobar lesions defines mixed location hemorrhages (MLH).
- Distinguishing CAA, MLH, and Alzheimer's disease (AD) is crucial for accurate diagnosis and treatment.
Purpose of the Study:
- To compare clinical, radiological, and cerebrospinal fluid (CSF) biomarker data in patients with CAA, MLH, AD, and healthy controls (HCs).
- To determine the position of MLH within the spectrum of cerebrovascular diseases.
- To investigate the relationship between CAA, MLH, and HTN-A.
Main Methods:
- Retrospective cohort study of 31 CAA, 31 MLH, 28 AD, and 30 HC patients.
- Analysis included clinical data, radiological findings, and CSF biomarkers (Aß42, Aß40, t-tau, p-tau).
- Histopathological data was also analyzed where available.
Main Results:
- Cortical superficial siderosis (cSS) was more frequent in CAA than MLH (45% vs 13%).
- CSF biomarker profiles showed HC > MLH > CAA > AD for Aß42 and Aß42/Aß40 ratio, and the reverse for t-tau and p-tau.
- Lower Aß40/Aß42 levels were observed in CAA and MLH patients with cSS and lacunar infarcts.
Conclusions:
- MLH and CAA are not mutually exclusive and likely represent points on a disease spectrum.
- MLH may involve contributions from both CAA and hypertensive arteriopathy (HTN-A).
- Understanding this spectrum aids in differentiating these common causes of hemorrhage in the elderly.
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.
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