Du et al. BMC Neurology
(2019) 19:97
https://doi.org/10.1186/s12883-019-1326-2

CASE REPORT

Open Access

Cerebral amyloid angiopathy-related
inflammation: a case report presenting with
a rare variant in SORL1 gene
Yanjiao Du1, Chao Liu1*, Congmin Ma1, Xiaohui Xu1, Xufeng Zhou2, Haitao Zhou1 and Chao Huang1

Abstract
Background: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare clinical entity, characterized by
headaches, seizures, rapidly progressive cognitive decline, behavioral changes and magnetic resonance imaging
(MRI) findings underlying the autoimmune and inflammatory reaction at the level of CAA-affected vessel. CAA-ri is
likely responsive to corticosteroid. MRI shows asymmetric and multifocal white matter hyperintensity (WMH) lesions
and multiple cerebral microbleeds. Apolipoprotein E (ApoE) ε4 homozygosity is associated with CAA-ri strongly
[Neurology 68(17):1411-1416, 2007, Ann Neurol 73(4):449-458, 2013, J Alzheimers Dis 44(4):1069-1074, 2015]. SORL1
processes a causal involvement in Alzheimer’s disease (AD) as a proposed modulator of the amyloid precursor
protein (APP). It is unclear whether SORL1 is involved with CAA-ri or not.
Case presentation: A 48-year-old woman suffered from a one-day history of a headache, nausea, and vomiting.
Neurological examination revealed normal. We diagnosed this case as probable CAA-ri according to the clinic
manifestations and MRI. Gene detection indicated a rare variant in SORL1 and ApoE ε4 homozygosity. When treated
with corticosteroid, the patient’s clinical symptoms and MRI manifestations were almost relieved. However, when
keeping the corticosteroid withdrawal for three months, the patient relapsed with a headache and typical images
on MRI emerged. Corticosteroid therapy was effective again. Unfortunately, susceptibility weighted imaging (SWI)
showed increased microbleeds. With tapering corticosteroid slowly, no recurrence was found on this patient with
four-month follow-up.
Conclusion: A variant of SORL1 may be associated with CAA-ri, recurrence of disease could be detected with MRI
by an increased microbleeds. Our case report suggests that corticosteroid therapy might be effective for CAA-ri.
Keywords: CAA-ri, ApoE, SORL1, Corticosteroid, Recurrence

Background
Cerebral amyloid angiopathy (CAA) is presented with
progressive deposition of amyloid proteins within the
cortical and leptomeningeal arteries, which is a common
pathology in the elder [1, 2]. In recent years, studies
show that coexisting inflammations found in CAA patients, such as vasculitis or perivasculitis, have been recognized as CAA-related inflammation (CAA-ri) [3].
CAA-ri is a rare clinical entity, characterized by headaches, seizures, rapidly progressive cognitive decline,
* Correspondence: liuchao-20001103@163.com
1
Department of Neurology, Luoyang Central Hospital Affiliated to
Zhengzhou University, NO. 288, Middle Zhongzhou Road, Xigong Square,
Luoyang 471000, China
Full list of author information is available at the end of the article

behavioral changes and MRI findings underlying the
autoimmune and inflammatory reaction at the level of
CAA-affected vessel [4–7]. CAA-ri is thought to result from an inflammatory response to β-amyloid
(Aβ) protein in the blood vessel walls [5] and likely
responsive to corticosteroid or other immunosuppressive agents [7]. According to the pathology, CAA-ri
can be divided into two subtypes. Inflammatory CAA is
perivascular infiltration around the vessel wall, and
Aβ-related angiitis is characterized by transmural and
intramural inflammation, often with gulomas formation
[8, 9]. Amyloid-related imaging abnormalities (ARIA)
represent the major severe side effect of Aβ immunotherapy for Alzheimer’s disease (AD), and characterize
the acute phase of CAA-ri [9]. Hence, this supports a

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Du et al. BMC Neurology

(2019) 19:97

hypothesis that an immunological response to vascular
amyloid, with increased vascular permeability, may be a
common underlying pathophysiological mechanism of
CAA-ri [10]. Apolipoprotein E (ApoE) ε4 homozygosity
known to associate with increased burden of Aβ deposition in vessels [11], is strongly associated with CAA-ri
[4, 5, 12]. In this case, we present a case of spontaneous
CAA-ri with a variant in SORL1, which emerges as a
promising candidate in control of the brain amyloidogenic processes in AD pathology [13] and with ApoE ε4
homozygosity.

Page 2 of 6

Case presentation
A 48-year-old woman presented to our outpatient neurology
with a headache, nausea, and vomiting for one day. Her
headache was persistent, tolerable and blunt in the right temporal region. She had a hypertension history for three years
and had been controlled within normal range by antihypertensive drugs. She had no psychosocial and familial hereditary history. Neurological examination was normal. Routine
blood tests, serum C-reactive protein level and erythrocyte
sedimentation rate showed normally. Serum thyroid hormone and sex hormone level were also in the normal range.

Fig. 1 Brain magnetic resonance imaging (MRI) findings of our patient at the onset, a-c multifocal white matter hyperintensity lesions were
revealed on T2 and fluid attenuated inversion recovery (FLAIR) and slight hypointense on T1 (arrows); d gadopentetate enhanced MRI showing
no lesion was enhanced; e: susceptibility weighted imaging (SWI) showing multiple cerebral microbleeds in cortical and subcortical areas; f
magnetic resonance spectrum demonstrating a normal spectrum in lesions; g magnetic resonance angiography was normal; h: magnetic
resonance venography showing thinness in the bilateral transverse and left sigmoid sinus and decreased signal intensity

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Page 3 of 6

Fig. 2 Gene detection results of the patient. a Apolipoprotein E ε4 homozygosity, b a variant in SORL1:c.4901A>T

Serum anti-MPO and P-ANCA were weakly positive, while
other indicators including antinuclear, anti-SSA, anti-SSB,
anti-dsDNA, anti-Sm, anti-RNP, anti-Scl-70, anti-RP3,
anti-GBM, anti-neutrophil cytoplasmic antibodies in cytoplasmic, antibodies to neuro-paraneoplastic syndromes, neuromyelitis optica (NMO), myelin basic protein (MBP) and
myelin oligodendrocyte glycoprotein (MOG) in blood as well
as cerebrospinal fluid (CSF) were negative. Serum tumor
markers were negative. Lumber puncture showed higher
intracranial pressure with 240 mmH2O. Subsequent CSF
analysis showed normal protein, glucose, and cell count.
Testing on the bacterial, viral, fungal and cryptococcal pathogens of CSF was negative. Magnetic resonance imaging
(MRI) of the brain revealed multifocal white matter hyperintensity (WMH) lesions (cortico-subcortical) on T2 and fluid
attenuated inversion recovery (FLAIR) associated mass effect,
which were slight hypointense on T1 and didn’t enhance on
gadopentetate enhanced MRI (Fig. 1a-d). Susceptibility

weighted imaging (SWI) revealed multiple cerebral microbleeds in cortical and subcortical areas (Fig. 1e). Magnetic
resonance spectrum (MRS) demonstrated a normal
spectrum. (Fig. 1f). Magnetic resonance angiography showed
normally (Fig. 1g). Magnetic resonance venogram showed
thinness in the bilateral transverse and left sigmoid sinus and
decreased signal intensity (Fig. 1h). Further digital subtraction angiography excluded venous sinus thrombosis. The
genetic sequencing showed ApoE ε4 homozygosity and a
variant in SORL1 (Fig. 2a-b).
Based on these findings, we made a diagnosis of probable CAA-ri. We firstly treated the patient with dexamethasone 10 mg/day via venous for three days and then
reduced it by half for three days, followed by oral prednisolone 60 mg/day tapered within six weeks (a weekly reduction of 10 mg). On the 3rd day of treatment, her
headache was significantly relieved. MRI demonstrated
that the lesions on FLAIR almost completely disappeared

Fig. 3 MRI findings after the first corticosteroid therapy. a FLAIR images showing lesions were almost completely disappeared; b SWI images
showing multiple cerebral microbleeds remained unchanged

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Fig. 4 Recurrence MRI images after corticosteroid withdrawal for three months. a multifocal white matter hyperintensity lesions were revealed on
FLAIR; b multiple cerebral microbleeds in cortical and subcortical areas increased on SWI

six weeks later (Fig. 3a-b). She presented to our clinic with
complaints of a headache again after corticosteroid withdrawal for three months. MRI indicated CAA-ri relapsed
and SWI showed that the microbleeds in cortical/subcortical areas were increased (Fig. 4a-b). We launched the
methylprednisolone 1000 mg pulse therapy for her. Lesions on T2/FLAIR disappeared quickly. We recommended reducing the dose of corticosteroid gradually
until a long-term administration of oral prednisone 5 mg/
day. No recurrence was found and the lesions of microbleeds were not increased any more over the next
four-month follow-up (Fig. 5a-b).

Discussion and conclusions
Definitive diagnosis of CAA-ri generally requires typical
clinical manifestation, typical MRI features, and brain

biopsy [8]. A study demonstrated image-guided stereotactic brain biopsy is usually safe, but complications may
occur, with transient and permanent morbidity in 9 and
13% of cases [14]. Considering the risk of brain biopsy,
Auriel, et al. validated the modified probable CAA-ri criteria, which is sufficiently specific to be incorporated
into the clinical practice for identifying patients with
good sensitivity and excellent specificity [15]. According
to the criteria [15], we made a diagnosis of probable
CAA-ri based on five aspects: (1) the patient’s age was
over 40 years old; (2) the patient presented with headache but no acute intracerebral hemorrhage (ICH) was
found; (3) MRI showed WMH lesions (cortico-subcortical) which were asymmetric without past ICH; (4) SWI
revealed multiple cerebral microbleeds in cortical and
subcortical areas; (5) No neoplastic, infectious or other

Fig. 5 MRI images after the second corticosteroid therapy for four months. a no lesion was found on FLAIR; b microbleeds were not increased
on SWI

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indications were found according to the laboratory and
imaging results. Lesions on T2/FLAIR revealed obvious
edema and no lesion was enhanced in MRI gadolinium
enhancement, which was similar to low-grade glioma
and lymphoma [16]. However, they were excluded by a
further MRS examination. The images of posterior reversible encephalopathy syndrome (PRES) was similar to
CAA-ri. But PRES is always accompanied by hypertension combined with severe underlying diseases, including high blood pressure, pregnancy eclampsia, severe
kidney disease, malignant tumor, systemic lupus erythematosus, etc. Due to the patient’s controlled normal
blood pressure and none of the diseases mentioned
above, we excluded PRES. The diagnosis of CAA-ri is
considered as definite if, in addition to these criteria, a
histopathologic examination indicates perivascular,
transmural, or intramural inflammation and amyloid deposition within vessels of the affected area in the cortex
and the leptomeninges [7]. However, our patient refused
to take a brain biopsy.
The best therapy of CAA-ri remains to be determined.
The presented data support to use the empirical immunosuppressive therapy (and avoiding brain biopsy) for patients who meet the criteria proposed for probable
CAA-ri [7, 15]. A reasonable subsequent approach would
be considered a brain biopsy in empirically treated patients who fail to respond to the corticosteroid therapy
within three weeks [7]. Strict blood pressure control was
also managed for patients with hypertension [17]. The primary treatment for our patient was dexamethasone 10 mg
per day via venous infusion. Clinical symptoms and image
almost completely relieved (Fig. 3). After keeping corticosteroid withdrawal for three months, the patient
developed recurrence. She was treated with high-dose
methylprednisolone, clinical symptoms and lesions on T2/
FLAIR were completely relieved, which supported the
diagnosis of CAA-ri [4, 6, 7]. When recurred, SWI showed
increased microbleeds in the cortical/subcortical areas
(Fig. 4). In the following four months, the lesions of
microbleeds have not been increased, indicating that the
microbleeds may be the result of the acute vascular inflammation of CAA-ri. To improve prognosis, large samples studies to further determine a better administration
for CAA-ri are necessary.
Genetic detection of the patient indicated ApoE ε4
homozygosity and a variant in SORL1 (chromosome11,
c.4901A>T) (Fig. 2), which was fairly rare in the normal
population. Strong support for a causal involvement in
neurodegenerative disease came with genetic studies associating SORL1 gene variants with the occurrence of
sporadic AD [13]. SORL1 encodes a 250-kDa protein
named sorting protein-related receptor with A-type repeats (SorLA), decreasing production and deposition of
Aβ peptide as a proposed modulator of amyloid

Page 5 of 6

precursor protein (APP) processing [13, 18]. Aβ levels
are mainly determined by the kinetic of SorLA and APP
interaction according to the mathematic model which
supports the fact that APP sorting pathway is a very important factor in defining the risk of AD [13, 19, 20].
CAA-ri is thought to result from an inflammatory response to Aβ protein in the blood vessel walls [5]. Spontaneous ARIA and CAA-ri have also been described in
familial forms of AD (FAD), i.e., in β-amyloid protein
precursor -amyloid protein precursor (AβPP) duplication
carriers [21], in presenilin 1-associated FAD (I202F
PSEN1 mutation) [12], and in two siblings carrying the
P284S PSEN1 mutation [22]. Thus, SORL1 may be associated with CAA-ri. A variant in SORL1 may give rise to
the risk of CAA-ri via immune response to Aβ excessive
deposition. ApoE ε4 homozygosity known to associate
with increased burden of Aβ deposition in vessels [11] is
strongly associated with CAA-ri [4, 5, 12] and may potentiate the intense inflammatory response [23]. Investigation of the degree of CAA-ri and inflammation in
SORL1 mutation with ApoE ε4 homozygosity would be
an interesting avenue for future research.
A variant of SORL1 may be associated with CAA-ri,
recurrence of disease could be detected with MRI by an
increased microbleeds. Our case report suggests that
corticosteroid therapy might be effective for CAA-ri.
Abbreviations
AD: Alzheimer’s disease; ApoE: apolipoprotein E; APP: amyloid precursor
protein.; ARIA: Amyloid-related imaging abnormalities; Aβ: β-amyloid;
AβPP: β-amyloid protein precursor; CAA: cerebral amyloid angiopathy,; CAAri: cerebral amyloid angiopathy-related inflammation; CSF: cerebrospinal fluid;
FLAIR: fluid attenuated inversion recovery; ICH: intracerebral hemorrhage;
MBP: myelin basic protein; MOG: myelin oligodendrocyte glycoprotein;
MRI: magnetic resonance imaging; MRS: magnetic resonance spectrum;
NMO: neuromyelitis optica; PRES: posterior reversible encephalopathy
syndrome; SorLA: sorting protein-related receptor with A-type repeats;
SWI: susceptibility weighted imaging; WMH: white matter hyperintensity

Acknowledgements
We thank the patient for data collection and Kangso medical inspection for
technical assistance. We thank Zhihui Duan, Yuezhen Han, Yan Li and
Yonggang Wang for making some useful suggestions on polishing the
manuscript.

Funding
None.

Availability of data and materials
All data and material supporting our findings are contained within the manuscript.

Authors’ contributions
YD was a major contributor in writing the manuscript. XZ, YD, CL and CM
analyzed clinical and MRI manifestations. HZ and CH analyzed gene
detection results. YD, CL, CM, XX, HZ and CH gave the clinical information
containing medical history, neurological and MRI image findings, gene
detection results and treatment. YD and CL contributed to editing and
revising the manuscript and supervised this publication. All authors read and
approved the final manuscript.

Du et al. BMC Neurology

(2019) 19:97

Ethics approval and consent to participate
The Institutional Review Board of Luoyang Central Hospital Affiliated to
Zhengzhou University approved this study. Informed consent for
participation was obtained from the patient.
Consent for publication
Written informed consent was obtained from the patient for publication of
this case report and any accompanying images. A copy of the consent is
available for review by the editor of this journal.
Competing interests
The authors declare no conflicts of interest with respect to the research,
authorship, funding, and/or publication of this article.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Department of Neurology, Luoyang Central Hospital Affiliated to
Zhengzhou University, NO. 288, Middle Zhongzhou Road, Xigong Square,
Luoyang 471000, China. 2Department of Radiology, Luoyang Central Hospital
Affiliated to Zhengzhou University, NO. 288, Middle Zhongzhou Road,
Xigong Square, Luoyang 471000, China.
Received: 29 September 2018 Accepted: 3 May 2019

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