These data suggest that deletion of apoA-I is associated with increased clearance of Aβ and reduced parenchymal and vascular Aβ pathology in the Tg2576 model.
A new genetic variant of hereditary apolipoprotein A-Iamyloidosis: a case-report followed by discussion of diagnostic challenges and therapeutic options.
In ApoA-I related amyloidosis involving the heart, amyloid deposits are mainly constituted by the 93-residue N-terminal region of the protein, here indicated as [1-93]ApoA-I.
Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-Iamyloidosis.
The decreased affinity of ApoA-I amyloidogenic variants for lipids, together with the increased efficiency in the cholesterol efflux process, could explain why, despite the unfavourable lipid profile, patients affected by ApoA-I related amyloidosis do not show a higher CVD risk.
Both of them were able to avoid the aggregation of Aβ in vitro, even though recombinant ApoA-I-M was significantly more effective in protecting endothelial cells from Aβ(1-42)-toxicity.
We checked and compared by fluorescence techniques the binding of human apolipoprotein A-I and a natural mutant involved in amyloidosis to the hydrogel scaffolds.
Case 1 was thus diagnosed as nonhereditary ApoA-1 associated renal amyloidosis with membranous nephropathy, and case 2 as hereditary ApoA-1amyloidosis with multiorgan injuries (kidney and spleen) and a positive family history.
In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations.
The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis.
ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007).
Mutations in human apolipoprotein A-I (apoA-I) are associated with low high-density lipoprotein (HDL) cholesterol levels and pathological conditions such as premature atherosclerosis and amyloidosis.
Apo AIamyloidosis is characterized by slowly progressive renal disease and end-stage renal disease occurs aproximately 3 to 15 years from initial diagnosis.
On the other hand, aortic stiffness was significantly greater in patients with APO A-I amyloidosis than controls (PWV 11.5 ± 2.9 and 10.7 ± 2.3 m/s, p < 0.05), even after adjusting for confounders.
The X-ray crystal structure of the C-terminal truncated human protein, Δ(185-243)apoA-I, determined to 2.2 Å resolution by Mei and Atkinson, provides the structural basis for understanding apoA-I destabilization in amyloidosis.
Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis.
The clinical spectrum and outcome of hereditary apolipoprotein A-Iamyloidosis are reviewed in detail and support the need for sequencing of the apolipoprotein A-I gene among patients with apparent localized amyloidosis in whom IHC is nondiagnostic of the fibril protein, even in the absence of a family history of disease.
ApoA-I variants with amino acid substitutions, especially in the region of amino acid residues 50-93 and 170-178, have been associated with amyloidosis.