Apolipoprotein AI-derived (AApoAI) amyloidosis may present either as a non-hereditary form with wildtype protein deposits in atherosclerotic plaques or as a hereditary form due to germline mutations in the APOA1 gene. Currently , more than 50 apoAI variants are known , and 13 are associated with amyloidosis. We describe six patients with AApoAI amyloidosis due to APOA1 germline mutations that affect the larynx, small intestine , large intestine , heart , liver , kidney, uterus , ovary , or pelvic lymph nodes. In each patient, the amyloid showed a characteristic apple green birefringence when viewed under polarized light after Congo red staining and was immunoreactive with antibodies against apoAI. Sequence analyses revealed one known (p.Leu75Pro) and three novel APOA1 mutations that included gene variations leading to two different frameshifts (p.Asn74fs and p.Ala154fs) and one amino acid exchange (p.Leu170Pro). These three novel mutations extend our knowledge about both the location of the mutations and the organ distribu

The carpal tunnel ligament often encloses transthyretin-derived (ATTR) amyloid deposits. In this study we tested the hypothesis that ATTR amyloid in the carpal tunnel ligament is most commonly of wildtype origin in a Caucasian population without endemic background of familial amyloid polyneuropathy. All resection specimens from the carpal tunnel ligament were retrieved from the Amyloid Registry of the University of Kiel spanning the period of 2004-2011 and dichotomized into two study groups: the first study group of 25 patients was obtained from diverse referring pathologists. The second group comprised a patient cohort of 73 patients obtained from a single-referring department of pathology. The selection of biopsies was based on the histological identification of amyloid by Congo red staining and polarization microscopy between crossed polars and immunohistochemical classification as ATTR amyloid. A novel anti-TTR-peptide antibody was raised in rabbits using a recombinant peptide (FHEHAEVVFTANDSGPRRYT) spanning residues 87-106 of the TTR protein. Amplification of the TTR exons 1, 2, 3 and 4 was done by a nested polymerase chain reaction approach. Ninety-eight biopsies were available from 98 patients, including 51 women and 47 men. All amyloid deposits showed strong immunoreactions with the novel anti-TTR peptide antibody. In 81 of 98 patients, genomic DNA was available. In 10 (12%) patients non-amyloidogenic TTR gene mutations were found with the following amino acid substitutions: p.G6S (normal allelic variant). A single patient carried a p.G6S and a p.M13I-variant. The remaining patients all showed wildtype sequence of the TTR gene (70 patients). No significant difference was found between the two study groups. ATTR amyloid in the carpal tunnel ligament is commonly of wildtype origin and genetic counseling is not mandatory in these patients.

No abstract

Hepatic amyloidosis is most commonly AL amyloid of lambda- and kappa-light chain origin and is often associated with marked parenchymal atrophy.

Although conformation-sensitive detection seemed promising, PTAA and B10 stain only a fraction of the examined amyloid samples when using routine surgical pathology settings. This study emphasises the necessity of having optimised pre-analytical protocols for recovery, storage and handling of samples if these novel amyloid ligands are to be used in routine diagnosis of amyloid.