Amyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders

Batarseh, Yazan S.; Duong, Quoc-Viet; Mousa, Youssef M.; Rihani, Sweilem B. Al; Elfakhri, Khaled H.; Kaddoumi, Amal

doi:10.3390/ijms17030338

Cited by 73 publications

(53 citation statements)

References 175 publications

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“…Astrocytes have been increasingly recognized as an important contributor to the neuroinflammatory and neurodegenerative processes in Aβ-related human disorders including CAA [19]. The accumulation of cerebral microvascular amyloid in rTg-DI rats similarly promotes a strong astroglial response in several ways.…”

Section: Resultsmentioning

confidence: 99%

Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy

Zhu

Hatfield

Sullivan

et al. 2020

J Neuroinflammation

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Background: Cerebral amyloid angiopathy (CAA) is a common cerebral small vessel disease of the aged and a prominent comorbidity of Alzheimer's disease (AD). CAA can promote a variety of vascular-related pathologies including neuroinflammation, cerebral infarction, and hemorrhages, which can all contribute to vascular cognitive impairment and dementia (VCID). Our understanding of the pathogenesis of CAA remains limited and further investigation of this condition requires better preclinical animal models that more accurately reflect the human disease. Recently, we generated a novel transgenic rat model for CAA (rTg-DI) that develops robust and progressive microvascular CAA, consistent microhemorrhages and behavioral deficits. Methods: In the current study, we investigated perivascular pathological processes that accompany the onset and progressive accumulation of microvascular CAA in this model. Cohorts of rTg-DI rats were aged to 3 months with the onset of CAA and to 12 months with advanced stage disease and then quantitatively analyzed for progression of CAA, perivascular glial activation, inflammatory markers, and perivascular stress. Results: The rTg-DI rats developed early-onset and robust accumulation of microvascular amyloid. As the disease progressed, rTg-DI rats exhibited increased numbers of astrocytes and activated microglia which were accompanied by expression of a distinct subset of inflammatory markers, perivascular pericyte degeneration, astrocytic caspase 3 activation, and disruption of neuronal axonal integrity. Conclusions: Taken together, these results demonstrate that rTg-DI rats faithfully mimic numerous aspects of human microvascular CAA and provide new experimental insight into the pathogenesis of neuroinflammation and perivascular stress associated with the onset and progression of this condition, suggesting new potential therapeutic targets for this condition. The rTg-DI rats provide an improved preclinical platform for developing new biomarkers and testing therapeutic strategies for microvascular CAA.

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Section: Resultsmentioning

confidence: 99%

Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy

Zhu

Hatfield

Sullivan

et al. 2020

J Neuroinflammation

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“…Localized amyloidoses range from Alzheimer's extracellular deposits to Huntington's intracellular tangles to rare amyloidoma masses . Only 7–12% of amyloid deposition causes amyloidomas .…”

Section: Introductionmentioning

confidence: 99%

“…2,4,5 Localized amyloidoses range from Alzheimer's extracellular deposits to Huntington's intracellular tangles to rare amyloidoma masses. 4,[6][7][8][9][10][11] Only 7-12% of amyloid deposition causes amyloidomas. 6,7 The absence of systemic symptoms and amyloidoma development in multiple organs provide evidence that these benign lesions likely are local amyloidoses.…”

Section: Introductionmentioning

confidence: 99%

Primary cervical spine AL‐κ amyloidoma: A case report and review of the literature

et al. 2019

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Of the myriad of variants of amyloidoses where abnormally folded proteins damage native tissue, primary cervical spine amyloidoma represents one of the rarest forms. Since clinical presentations and imaging findings appear similar to other pathologies, including abscesses, metastatic lesions, and inflammatory lesions, a definitive diagnosis requires a biopsy with specific immunohistochemical stains. We present the first known case of primary cervical amyloid light‐chain (AL)‐κ subtype amyloidoma and compare the clinical presentations, imaging findings, treatment options, and immunohistochemical subtypes of primary, hemodialysis, and multiple myeloma cervical amyloidomas. Our case is of a 58‐year‐old man who developed neck pain radiating to the left arm with bilateral upper extremity weakness over several months. Magnetic resonance imaging revealed a circumferential C1–C2 mass extending into the neural foramina inducing severe mass effect. The patient underwent C2 laminectomy and resection of the lesion which was discovered during surgery to be completely epidural. Postoperatively, his pain and weakness improved. A complete work‐up was negative for systemic amyloidosis or inflammatory conditions. In the setting of a long clinical history of hemodialysis, this patient required specific staining and laboratory testing to correctly diagnose his primary cervical AL‐κ subtype amyloidoma. Cervical amyloidomas comprise a very small minority of amyloid pathology with an exceptional prognosis following successful surgical resection and stabilization. It is recommended these patients undergo surgical resection with appropriate characterization and a complete work‐up to rule out systemic disease.

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“…Astrocytes are glial cells known for their star-like appearance and play a key role in neurological diseases (Batarseh et al, 2016). Astrocytes anatomical location is distinctive being near brain blood vessels, and play a major role in maintaining the BBB integrity (Abbott, 2002).…”

Section: Introductionmentioning

confidence: 99%

Oleocanthal ameliorates amyloid-β oligomers’ toxicity on astrocytes and neuronal cells: In vitro studies

et al. 2017

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Extra-virgin olive oil (EVOO) has several health promoting effects. Evidence have shown that EVOO attenuates the pathology of amyloid-β (Aβ) and improves cognitive function in experimental animal models, suggesting it’s potential to protect and reduce the risk of developing Alzheimer’s disease (AD). Available studies have linked this beneficial effect to oleocanthal, one of the active components in EVOO. The effect of oleocanthal against AD pathology has been linked to its ability to attenuate Aβ and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type and AD transgenic mice in vivo. However, the ability of oleocanthal to alter the toxic effect of Aβ on brain parenchymal cells is unknown. In the current study, we investigated oleocanthal effect on modulating Aβ oligomers (Aβo) pathological events in neurons and astrocytes. Our findings demonstrated oleocanthal prevented Aβo-induced synaptic proteins, SNAP-25 and PSD-95, down-regulation in neurons, and attenuated Aβo-induced inflammation, glutamine transporter (GLT1) and glucose transporter (GLUT1) down-regulation in astrocytes. Aβo-induced inflammation was characterized by interleukin-6 (IL-6) increase and glial fibrillary acidic protein (GFAP) upregulation that were reduced by oleocanthal. In conclusion, this study provides further evidence to support the protective effect of EVOO-derived phenolic secoiridoid oleocanthal against AD pathology.

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Amyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders

Cited by 73 publications

References 175 publications

Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy

Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy

Primary cervical spine AL‐κ amyloidoma: A case report and review of the literature

Oleocanthal ameliorates amyloid-β oligomers’ toxicity on astrocytes and neuronal cells: In vitro studies

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