Mass Spectrophotometric Analysis of Focal Neural Amyloid Deposition Reveals Isolated Non-Mutated ApoA1 Amylodosis (IN1-1.009)

Abstract

Objective: Amyloidogenic molecules are normally ubiquitous circulating proteins, and the mechanism leading to amyloid transformation in vivo is not well understood. Amyloidomas represent a rare focal mass deposition of amyloid that may occur in peripheral nervous system tissues. We investigate a case of lumbosacral plexus amyloidoma, having unusual composition of amyloid, raising questions of pathogenesis. Background Mass spectrometry analysis defines specific amyloid types, distinguishing AL-amyloidosis from inherited apolipoprotein A1 (ApoA1), gelsolin (GEL), and transthyretin (TTR) varieties. Non-mutated ApoA1 and TTR amyloid deposition has been reported in the heart and blood vessels. SAP and ApoE are associated proteins of AL-amyloidosis. AL-light chain amyloidosis has presented with root and plexus amyloidomas having associated localized neurologic deficits. Design/Methods: A 46 yo male presented with insidious right lower extremity weakness with MRI imaging revealing an expansile mass within the lumbosacral roots and plexus including the sciatic nerve. Multiple serum, urine, and bone marrow analyses revealed no evident monoclonal gammopathy or plasma cell dyscrasia. He had no family history suggestive of systemic or neural amyloidosis. Targeted sciatic notch fascicular nerve biopsy with mass spectrometry analysis was performed. Results: The biopsied neural tissue stained positive with Congo red having apple-green birefringence, and immunostains for amyloid type were ambiguous. Laser microdissection mass spectrometry analysis of amyloid deposits demonstrated the predominant protein to be wild type ApoA1. DNA sequencing of the entire reading frame of ApoA1 was normal. Conclusions: Focal neural deposition of non-mutated ApoA1 predominant amyloid may occur. Discovery of unusual amyloid variants may be made possible by mass spectrometry analysis. Disclosure: Dr. Loavenbruck has nothing to disclose. Dr. Chaudhry has received personal compensation for activities with Novartis. Dr. Chaudhry has received personal compensation in an editorial capacity for the Neurologist. Dr. Chaudhry has received royalty payments from Abbott Laboratories, Inc. and Johnson & Johnson. Dr. Zeldenrust has nothing to disclose. Dr. Theis has nothing to disclose. Dr. Klein has received personal compensation for activities with Pfizer Inc as a consultant.