Cerebrovascular involvement in systemic AA and AL amyloidosis: a clear haematogenic pattern

Abstract

Amyloid deposits in cerebral vessels are common in beta-amyloid diseases (Alzheimer's disease, congophilic amyloid angiopathy, Down's syndrome and hereditary cerebral amyloidosis with haemorrhage of the Dutch type). We report of 20 autopsies on patients who had died with systemic amyloidosis of the AA, Alambda and Akappa types: the brains were examined for the occurrence of amyloid. Vascular amyloid was detected in choroid plexus (in 17 of 20 cases), infundibulum (5 of 8), area postrema (6 of 11), pineal body (3 of 7) and subfornical organ (2 of 3), but not in cortical and leptomeningeal vessels. Immunohistochemical classification of the cerebral amyloid and the systemic amyloid syndrome showed identity proving the same origin of both. The distribution is indicative of a haematogenic pattern of amyloid deposition in systemic amyloidosis and is different from that in Alzheimer's, prion, ATTR and cystatin C diseases. It corresponds to areas of the brain with a "leaky" blood-brain barrier. Additionally, all the cases with AA amyloidosis exhibited an Abeta coreactivity in choroid plexus vessels. In one exceptional case, Abeta reactivity of AA amyloid also occurred outside of the brain.

Multiplexed Proteomic Analysis of Oxidation and Concentrations of Cerebrospinal Fluid Proteins in Alzheimer Disease

“…Chains, also known as immunoglobulin light chains, are involved in systemic and localized primary immunoglobulin-related (amyloid light chain or AL) amyloidosis (34,35 ). Interestingly, immunohistopathological studies have indicated that chains may be associated with amyloid deposits (36,37 ), whereas IgG and IgM have been shown to deposit in epithelial basement membrane of choroid plexus in AD brain (38 ).…”

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

“…Decreased Ab clearance was shown in the brains of patients with AD (Bading et al 2002;Ghribi et al 2006;Jaeger et al 2009a;Levy et al 2006). More than 30% of patients with AD present cerebrovascular pathology involving cellular elements from BBB structure (Schroder and Linke 1999). The neurovascular hypothesis states that brain Ab concentrations are regulated by rapid RAGE and LRP-mediated transport at the BBB (Deane et al 2004;Hong et al 2009;Liu et al 2009a).…”

Subcellular localization of nicotinamide adenine dinucleotide phosphate oxidase subunits in neurons and astroglia of the rat medial nucleus tractus solitarius: Relationship with tyrosine hydroxylase immunoreactive neurons

“…In addition, the presence of phox proteins in diverse cellular compartments of mNTS neurons and glia supports a structural basis for the emerging role of redox modulation of autonomic, and particularly cardiovascular processes. Moreover, given the important role of ROS, dorsal vagal pathology, and autonomic dysfunction in neurological disease, aberrant free radical production in the NTS may be a potential candidate substrate of dorsal vagal damage accompanying sudden infant death syndrome (Sparks et al, 1996, Biondo et al, 2004, myocardial infarction (De Caro et al, 2000), as well as several major neurological disorders (Saper et al, 1991, Schroder and Linke, 1999, Dewey, 2004 Light microscopic immunoperoxidase labeling for p47 phox in the dorsal vagal complex. At the top left, a schematic figure representing the brainstem level sampled in the present study is provided for orientation.…”