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.

AA Amyloid Deposition in the Central and Peripheral Nervous Systems in Flamingos

“…AA deposition in periventricular blood vessels associated with systemic AA amyloidosis has been reported only once in humans, and the etiology is suggested to involve a leaky blood-brain barrier in circumventricular organs. 25 In this study, cerebrovascular AA deposition was observed only in periventricular vessels, suggesting that the specific structure of periventricular blood vessels may be related to this pathologic process.…”

AA Amyloid Deposition in the Central and Peripheral Nervous Systems in Flamingos

“…AA deposition in periventricular blood vessels associated with systemic AA amyloidosis has been reported only once in humans, and the etiology is suggested to involve a leaky blood-brain barrier in circumventricular organs. 25 In this study, cerebrovascular AA deposition was observed only in periventricular vessels, suggesting that the specific structure of periventricular blood vessels may be related to this pathologic process.…”

Mechanisms of Cerebrovascular Amyloid Deposition: Lessons from Mouse Models

“…27 This distribution corresponds to areas with incomplete BBB, consistent with a hematogenic origin of AA and AL. 27 This pattern, however, is different from that in Aβ-CAA where mainly cortical and leptomeningeal vessels are affected.…”

A 44‐Year‐Old Female with Familial Mediterranean Fever, Cardiomyopathy and End Stage Renal Disease

“…This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3). A notable exception is systemic ATTR amyloidosis in which the abnormal protein is synthesized by both the liver and choroid plexus, with diffuse involvement of the vessels of the leptomeninges, cortex and choroid plexus (2).…”

“…It had previously been thought that systemic amyloidosis rarely involved the brain, based on routine examination of the leptomeningeal, cortical and basal vasculature. However, later investigators have demonstrated that in systemic amyloidosis, amyloid is commonly seen in areas that lack an intact blood-brain barrier, including the choroid plexus, infundibulum and area postrema, although not in the meningocortical vasculature (2). This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3).…”

AA Amyloid Deposition in the Central and Peripheral Nervous Systems in Flamingos

“…AA deposition in periventricular blood vessels associated with systemic AA amyloidosis has been reported only once in humans, and the etiology is suggested to involve a leaky blood-brain barrier in circumventricular organs. 25 In this study, cerebrovascular AA deposition was observed only in periventricular vessels, suggesting that the specific structure of periventricular blood vessels may be related to this pathologic process.…”

Mechanisms of Cerebrovascular Amyloid Deposition: Lessons from Mouse Models

“…27 This distribution corresponds to areas with incomplete BBB, consistent with a hematogenic origin of AA and AL. 27 This pattern, however, is different from that in Aβ-CAA where mainly cortical and leptomeningeal vessels are affected.…”

A 44‐Year‐Old Female with Familial Mediterranean Fever, Cardiomyopathy and End Stage Renal Disease

“…This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3). A notable exception is systemic ATTR amyloidosis in which the abnormal protein is synthesized by both the liver and choroid plexus, with diffuse involvement of the vessels of the leptomeninges, cortex and choroid plexus (2).…”

“…It had previously been thought that systemic amyloidosis rarely involved the brain, based on routine examination of the leptomeningeal, cortical and basal vasculature. However, later investigators have demonstrated that in systemic amyloidosis, amyloid is commonly seen in areas that lack an intact blood-brain barrier, including the choroid plexus, infundibulum and area postrema, although not in the meningocortical vasculature (2). This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3).…”

AA Amyloid Deposition in the Central and Peripheral Nervous Systems in Flamingos

“…AA deposition in periventricular blood vessels associated with systemic AA amyloidosis has been reported only once in humans, and the etiology is suggested to involve a leaky blood-brain barrier in circumventricular organs. 25 In this study, cerebrovascular AA deposition was observed only in periventricular vessels, suggesting that the specific structure of periventricular blood vessels may be related to this pathologic process.…”

Mechanisms of Cerebrovascular Amyloid Deposition: Lessons from Mouse Models

“…27 This distribution corresponds to areas with incomplete BBB, consistent with a hematogenic origin of AA and AL. 27 This pattern, however, is different from that in Aβ-CAA where mainly cortical and leptomeningeal vessels are affected.…”

A 44‐Year‐Old Female with Familial Mediterranean Fever, Cardiomyopathy and End Stage Renal Disease

“…This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3). A notable exception is systemic ATTR amyloidosis in which the abnormal protein is synthesized by both the liver and choroid plexus, with diffuse involvement of the vessels of the leptomeninges, cortex and choroid plexus (2).…”

“…It had previously been thought that systemic amyloidosis rarely involved the brain, based on routine examination of the leptomeningeal, cortical and basal vasculature. However, later investigators have demonstrated that in systemic amyloidosis, amyloid is commonly seen in areas that lack an intact blood-brain barrier, including the choroid plexus, infundibulum and area postrema, although not in the meningocortical vasculature (2). This is in contrast to the distribution of amyloid deposition in cerebral amyloid angiopathy (CAA) which preferentially involves the meningocortical vessels and rarely involves the subcortical white matter vessels, deep gray matter or brainstem (3).…”