A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

Nakagawa, Kazuma; Sheikh, Sarah; Snuderl, Matija; Frosch, Matthew P.; Greenberg, Steven M.

doi:10.1016/j.jns.2008.05.014

Cited by 31 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fact that similar FNEs have been recognised in forms of ATTR with extensive meningeal-vascular TTR deposition not only suggests that CNS ATTR deposition may play an important role in the emergence of FNEs, but also supports our findings in the ATTR-V30M patients 10 11 29–31. Additionally, in a recent study on sporadic CAA—a type of CNS Aβ vascular amyloid pathology that involves brain superficial blood vessels—the authors found that Aβ-CAA patients presented similar FNEs 32.…”

Section: Discussionsupporting

confidence: 88%

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Maia

Magalhães

Freitas

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

110

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 88%

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Maia

Magalhães

Freitas

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

110

View full text Add to dashboard Cite

show abstract

“…1 CAA can be caused not only by TTR but also by other amyloidogenic proteins/peptides such as amyloid- β , cystatin C, aDan and aBri. 28 Twelve different naturally occurring mutant forms of TTR have been found to be associated with OA, 29, 30, 31, 32, 33 and common variants such as V30M TTR, which is mainly associated with sympathetic and autonomic neuropathy, have been shown to cause OA in patients who received liver transplants. 3, 4 Liver transplantation is a clinically established procedure for removing mutant protein from the blood, 34 but not from the CNS, as TTR is also produced by the choroid plexus epithelia, hippocampal and cortical neurons.…”

Section: Discussionmentioning

confidence: 99%

Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis

et al. 2013

View full text Add to dashboard Cite

Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.

show abstract

“…EGCG may have a more ‘generic’ role, being cited in the management of AL amyloidosis110 and the neurodegenerative aggregations of amyloid-β and α-synuclein, responsible in part for Alzheimer’s and Parkinson’s disease 111. Of note, there are approximately 10 variants of TTR associated with amyloid deposition in the brain and CNS 112. EGCG presents an attractive treatment option given its human bioavailability of 39%, ability to cross the blood–brain barrier, and excellent tolerability.…”

Section: Treatment Of Ttr Amyloidosismentioning

confidence: 99%

The transthyretin amyloidoses: advances in therapy

Dubrey

Ackermann

Gillmore

2015

Postgraduate Medical Journal

View full text Add to dashboard Cite

There are two forms of transthyretin (TTR) amyloidosis: non-hereditary and hereditary. The non-hereditary form (ATTRwt) is caused by native or wild-type TTR and was previously referred to as senile systemic amyloidosis. The hereditary form (ATTRm) is caused by variant TTR which results from a genetic mutation of TTR. The predominant effect of ATTRwt amyloidosis is on the heart, with patients having a greater left ventricular wall thickness at presentation than the devastating form which is light chain (AL) amyloidosis. ATTRm amyloidosis is broadly split into two categories: a type that predominantly affects the nervous system (often called familial amyloid polyneuropathy (FAP)) and one with a predilection for the heart (often called familial amyloid cardiomyopathy (FAC)). Approximately half of all TTR mutations known to express a clinical phenotype cause a cardiomyopathy. Since the introduction of orthotopic liver transplantation for ATTRm amyloidosis in 1991, several additional therapies have been developed. These therapies aim to provide a reduction or elimination of TTR from the plasma (through genetic approaches), stabilisation of the TTR molecule (to prevent deposition) and dissolution of the amyloid matrix. We describe the latest developments in these approaches to management, many of which are also applicable to wild-type amyloidosis.

show abstract

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

Cited by 31 publications

References 20 publications

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis

The transthyretin amyloidoses: advances in therapy

Contact Info

Product

Resources

About