Amyloidosis of the Brain and Heart

Schaich, Christopher L.; Maurer, Mathew S.; Nadkarni, Neelesh K.

doi:10.1016/j.jchf.2018.12.014

Cited by 7 publications

(3 citation statements)

References 11 publications

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“…Additionally, neurofibrillary tangles have been shown to coexist with higher glutaminase activity 46 . The hypomethylated site in the transcription start site of the GLS gene may indicate its potential involvement in the central nervous system, which supports the recent finding of cerebral amyloid angiopathy in individuals with mutated TTR cardiac amyloidosis 47 . FAM129B (aliases; MEG-3 and NIBAN2 ) is downregulated in tissues with amyloid deposition and animal studies have shown that enhancing the expression of FAM129B reduces oxidative damage by reducing amyloid-beta production via PI3K/Akt signaling 48 .…”

Section: Discussionsupporting

confidence: 82%

Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

Pathak

Wendt

Lillo

et al. 2020

Preprint

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The Val122Ile mutation in Transthyretin (TTR) gene causes a rare, difficult to diagnose hereditary form of cardiac amyloidosis. This mutation is most common in the United States and mainly present in people of African descent. The carriers have an increased risk of congestive heart failure and several other non-cardiac phenotypes such as carpal tunnel syndrome, peripheral edema, and arthroplasty which are top reasons for ambulatory/outpatient surgeries in the country. We conducted first-ever epigenome-wide association study in Val122Ile carriers of African descent for heart disease (HD) and multiple outpatient surgeries (OS)- an early disease indicator. Five differentially methylated sites (p≤ ;2.1e-08) in genes FAM129B, SKI, WDR27, GLS, and an intergenic site near RP11-550A5.2 and one differentially methylated region containing KCNA6 and GALNT3 (p=1.1e-12) were associated with HD. For OS, we observe four sites, two sites in UBE2E3 and SEC14L5, and other two in intergenic regions (p ≤ ;1.8e-07) and three regions overlapping SH3D21, EVA1B, LTB4R2 and CIDEB (p ≤ ;3.9e-07). Functional PPI module analysis identified ABCA1 (p=0.001) for HS. Six cis-mQTLs were associated with one of the significant CpG sites (FAM129B; p=4.1e-24). We replicated two CpG sites (cg18546846 and cg06641417; p<0.05) in an external cohort of biopsy- confirmed cases of TTR amyloidosis. The genes identified are involved in transport and clearance of amyloid deposits (GLS, ABCA1, FAM129B); cardiac fibrosis (SKI); and muscle tissue regulation (SKI, FAM129B). These findings highlight the link between a complex amyloid circuit and diverse symptoms of Val122Ile.

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Section: Discussionsupporting

confidence: 82%

Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

Pathak

Wendt

Lillo

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…First, Ab has been found to accumulate in the heart of patients with AD and induce ADrelated cardiac amyloidosis, 5,6 findings raising a novel hypothesis that Ab disorder is a multiple organ syndrome. Second, the toxic effects of Ab preamyloid oligomers on cardiomyocytes have been demonstrated, causally linking cardiac Ab-amyloidosis with cardiac dysfunction.…”

mentioning

confidence: 99%

Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population

Zhu

Wolters

Yaqub

et al. 2023

JACC: Heart Failure

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“…Vessels for Aβ deposition include leptomeningeal and cortical vessels in CAA, cerebral microvessels, intracerebral arteries/Willis, aorta, and coronary/extracerebral arteries (Stakos et al, 2020). Aβ deposits can be found in the cardiac tissue of AD patients, and these deposits are related to the pathogenesis of CA (Schaich et al, 2019). From the perspective of tissue distribution, the accumulation of Aβ in the brain tissues of patients with AD or CAA is much higher than that in the heart of CA patients (Troncone et al, 2016).…”

Section: The Role Of Aβ In the Pathogenesis Of Caa/ad And Camentioning

confidence: 99%

Cerebral amyloid angiopathy-related cardiac injury: Focus on cardiac cell death

Zhang

2023

Front. Cell Dev. Biol.

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Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of the brain, causing cerebrovascular and brain parenchymal damage. CAA patients are often accompanied by cardiac injury, involving Aβ, tau and transthyroxine amyloid (ATTR). Aβ is the main injury factor of CAA, which can accelerate the formation of coronary artery atherosclerosis, aortic valve osteogenesis calcification and cardiomyocytes basophilic degeneration. In the early stage of CAA (pre-stroke), the accompanying locus coeruleus (LC) amyloidosis, vasculitis and circulating Aβ will induce first hit to the heart. When the CAA progresses to an advanced stage and causes a cerebral hemorrhage, the hemorrhage leads to autonomic nervous function disturbance, catecholamine surges, and systemic inflammation reaction, which can deal the second hit to the heart. Based on the brain-heart axis, CAA and its associated cardiac injury can create a vicious cycle that accelerates the progression of each other.

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Amyloidosis of the Brain and Heart

Cited by 7 publications

References 11 publications

Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population

Cerebral amyloid angiopathy-related cardiac injury: Focus on cardiac cell death

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