Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy

Bonaterra-Pastra, Anna; Benı́tez, Sònia; Pancorbo, Olalla; Rodríguez‐Luna, David; Vert, Carla; Freijó, Marimar; Tur, Sílvia; Martínez-Zabaleta, Maite; Portela, Pere Cardona; Vera, Rocío; Lebrato-Hernández, Lucia; Arenillas, Juan F.; Pérez-Sánchez, Soledad; Domínguez-Mayoral, Ana; Fàbregas, Joan Martí; Mauri, Gerard; Montaner, Joan; Sánchez-Quesada, José Luís; Hernández-Guillamón, Mar

doi:10.3389/fnagi.2023.1134399

Cited by 4 publications

(1 citation statement)

References 85 publications

(108 reference statements)

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“…In addition to Apo D, Apo E and Apo J are two other proteins that highlight the involvement of lipid metabolism in CAA. A study of 60 patients with lobar ICH tried to find the connection between imaging biomarkers of CAA with Apo D and Apo E. Lower levels of Apo E and Apo J in low-density lipoproteins (LDL) fractions of the blood samples showed an association with the cSS extent and CSO-EPVS, respectively (Bonaterra-Pastra et al, 2023).…”

Section: Apolipoproteinsmentioning

confidence: 99%

Fluid biomarkers in cerebral amyloid angiopathy

Savar,

Ma,

Hone

et al. 2024

Front. Neurosci.

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Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers as they do not require a procedure as invasive as a lumbar puncture. This article aimed to provide an overview of the present clinical data concerning fluid biomarkers associated with CAA and point out the direction of future studies. Among all the biomarkers discussed, amyloid β, neurofilament light chain, matrix metalloproteinases, complement 3, uric acid, and lactadherin demonstrated the most promising evidence. However, the field of fluid biomarkers for CAA is an under-researched area, and in most cases, there are only one or two studies on each of the biomarkers mentioned in this review. Additionally, a small sample size is a common limitation of the discussed studies. Hence, it is hard to reach a solid conclusion on the clinical significance of each biomarker at different stages of the disease or in various subpopulations of CAA. In order to overcome this issue, larger longitudinal and multicentered studies are needed.

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Section: Apolipoproteinsmentioning

confidence: 99%

Fluid biomarkers in cerebral amyloid angiopathy

Savar,

Ma,

Hone

et al. 2024

Front. Neurosci.

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Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches

Gholami

2023

Neuroscience Letters

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The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy

Bonaterra-Pastra,

Solé,

Lope-Piedrafita

et al. 2024

Alz Res Therapy

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Background Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA. Methods Twenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) (n = 9) or saline (n = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline (n = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings. Results rhApoJ-treated APP23 presented fewer cortical CMBs (50–300 μm diameter) (p = 0.012) and cortical larger hemorrhages (> 300 μm) (p = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation (p = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice (p = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα (p = 0.035) and MIP-1α (p = 0.035) levels, while lower MMP-12 (p = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume (p = 0.040) and irregular ICH shape (p = 0.036). Conclusions Chronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation.

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Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy

Cited by 4 publications

References 85 publications

Fluid biomarkers in cerebral amyloid angiopathy

Fluid biomarkers in cerebral amyloid angiopathy

Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches

The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy

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