Congophilic angiopathy
Encyclopedia
Cerebral amyloid angiopathy (CAA), also known as congophilic angiopathy, is a form of angiopathy
in which amyloid
deposits form in the walls of the blood vessels of the central nervous system. The term congophilic is used because the presence of the abnormal aggregations of amyloid
can be demonstrated by microscopic examination of brain tissue
after application of a special stain called Congo red
. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis
.
and cerebral vessel walls.
The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide and abnormal clearance having been proposed as potential causes. Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis
by astrocyte
s and microglia
l cells, (2) enzymatic degradation by neprilysin
or insulysin
(3) cleared by way of the blood brain barrier
or (4) drained along periarterial spaces. Abnormalities in each of these identified clearance pathways have been linked to CAA.
In familial forms of CAA the cause of Aβ build up is likely due to increased production rather than poor clearance. Mutations in the amyloid precursor protein
(APP), Presenilin
(PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ.
An immune mechanism has also been proposed.
. The hemorrhage within the brain is usually confined to a particular lobe and this is slightly different compared to brain hemorrhages which occur as a consequence of high blood pressure (hypertension
) - a more common cause of a hemorrhagic stroke (or cerebral hemorrhage).
Susceptibility weighted imaging
has been proposed as a tool for identifying CAA-related microhemorrhages.
Biopsies
also play a role in diagnosing the condition.
. This form has been associated with "Abeta-related angiitis".
However, there are other types:
Research is currently being conducted to determine if there is a link between cerebral amyloid angiopathy and ingestion of excessive quantities of aluminium, as occurred in the Camelford water pollution incident
.
Angiopathy
Angiopathy is the generic term for a disease of the blood vessels . The best known and most prevalent angiopathy is diabetic angiopathy, a common complication of chronic diabetes.-By caliber:...
in which amyloid
Amyloid
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...
deposits form in the walls of the blood vessels of the central nervous system. The term congophilic is used because the presence of the abnormal aggregations of amyloid
Amyloid
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...
can be demonstrated by microscopic examination of brain tissue
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
after application of a special stain called Congo red
Congo red
Congo red is the sodium salt of 3,3'-bis. It is a secondary diazo dye...
. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
.
Causes
CAA has been identified as occurring either sporadically (generally in elderly populations) or in familial forms such as Flemish, Iowa, and Dutch types. Sporadic forms of CAA have been further characterized into two types based on deposition of amyloid β-protein (Aβ) in cortical capillaries. In all cases it is defined by the deposition of Aβ in the leptomeningalLeptomeninges
In medicine, leptomeninges is a term used to refer to the pia mater and arachnoid mater, two of the membranes that surround the brain and the spinal cord....
and cerebral vessel walls.
The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide and abnormal clearance having been proposed as potential causes. Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
by astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
l cells, (2) enzymatic degradation by neprilysin
Neprilysin
Neprilysin, also known as membrane metallo-endopeptidase, neutral endopeptidase , CD10, and common acute lymphoblastic leukemia antigen , is a zinc-dependent metalloprotease enzyme that degrades a number of small secreted peptides, most notably the amyloid beta peptide whose abnormal misfolding and...
or insulysin
Insulin degrading enzyme
Insulin-degrading enzyme, also known as IDE is a human enzyme.Known alternatively as insulysin or insulin protease, Insulin Degrading Enzyme is a large zinc-binding protease of the M16A metalloprotease subfamily known to cleave multiple short polypeptides that vary considerably in sequence...
(3) cleared by way of the blood brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
or (4) drained along periarterial spaces. Abnormalities in each of these identified clearance pathways have been linked to CAA.
In familial forms of CAA the cause of Aβ build up is likely due to increased production rather than poor clearance. Mutations in the amyloid precursor protein
Amyloid precursor protein
Amyloid precursor protein is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export...
(APP), Presenilin
Presenilin
Presenilins are a family of related multi-pass transmembrane proteins that function as a part of the gamma-secretase intramembrane protease complex...
(PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ.
An immune mechanism has also been proposed.
Presentation
Amyloid deposition predisposes these blood vessels to failure, increasing the risk of a hemorrhagic stroke. Since this can be caused by the same amyloid protein that is associated with Alzheimer's dementia such brain hemorrhages are more common in people who suffer from Alzheimer's, however they can also occur in those who have no history of dementiaDementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
. The hemorrhage within the brain is usually confined to a particular lobe and this is slightly different compared to brain hemorrhages which occur as a consequence of high blood pressure (hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
) - a more common cause of a hemorrhagic stroke (or cerebral hemorrhage).
Diagnosis
Susceptibility weighted imaging
Susceptibility weighted imaging , originally called BOLD venographic imaging, uses a type of contrast in magnetic resonance imaging different from traditional spin density, T1, or T2 imaging. SWI uses a fully flow compensated, long echo, gradient echo scan to acquire images...
has been proposed as a tool for identifying CAA-related microhemorrhages.
Biopsies
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
also play a role in diagnosing the condition.
Types
It is usually associated with amyloid betaAmyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
. This form has been associated with "Abeta-related angiitis".
However, there are other types:
- the "Icelandic type" is associated with Cystatin CCystatin CCystatin C or cystatin 3 , a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease...
. - the "British type" is associated with ITM2BITM2BIntegral membrane protein 2B is a protein that in humans is encoded by the ITM2B gene.ITM2B or BRI2 is a gene located on chromosom 13. The gene is connected to Familial Danish Disease and Familial British Disease causing amyloid and pre-filbrillar effects similar to those seen in Alzheimers...
(also known as "BRI").
Research is currently being conducted to determine if there is a link between cerebral amyloid angiopathy and ingestion of excessive quantities of aluminium, as occurred in the Camelford water pollution incident
Camelford water pollution incident
The Camelford water pollution incident involved the accidental contamination of the drinking water supply to the town of Camelford, Cornwall, England with 20 tonnes of aluminium sulphate in July 1988...
.