Amyloid angiopathy

amyloid angiopathyAmyloid angiopathy (congophilic angiopathy) is a condition caused by the deposition of β-amyloid in the arteries (and sometimes veins) of the brain and spinal cord.


Description


Amyloidosis is a specific rare disease characterized by the accumulation of the abnormal protein called amyloid angiopathy in various organs. There are several different types of amyloid angiopathy. In cerebral amyloid angiopathy β-amyloid is stored in the walls of the vessels of the cerebral cortex and meninges of the spinal cord (membranes which overlay the spinal cord). Usually small and mid-size arteries are affected, less commonly vein are also involved.

β-amyloid may be found in the vessels of the elderly (may be asymptomatic) and especially those who suffer from Alzheimer disease.

The vessels with depositions of amyloid angiopathy are fragile and tend to rupture, causing lobe hemorrhagic stroke. Thickened vessel wall decreases the blood supply to the brain cortex and therefore results in dementia.

The alternative name for CAA is congophillic angiopathy due to the stain Congo used to see the amyloid angiopathy deposits during microscopy.


Causes
The causes of amyloid angiopathy deposition in the walls of the vessels are unknown, although sometimes the hereditary pattern is present and familial cases of CAA are possible.


Risk factors

People at the age of 55-60  and older are more likely to develop CAA. It is supposed that about 50% of elderly have CAA, although not always appear the symptoms.

Several genes such as the apolipoprotein E gene, transforming growth factor (TGF)-β1, presenilin 1 (PS1), α1-antichymotrypsin (ACT), neprilysin, low-density lipoprotein-receptor related protein (LRP-1), and angiotensin-converting enzyme (ACE) genes were reported to increase the risk of CAA.

Hypertension is also considered to be a risk factor for CAA.


Forms of CAA

CAA can be both sporadic or familial.

Sporadic CAA is not related to systemic amyloidosis and commonly solely brain vessels are involved.

Familial CAA is usually inherited as an autosomal dominant pattern. As opposed to the sporadic CAA familial CAA is characterized by the early onset of the disorder and the involvement of other body parts not only the cerebral vessels.

 

Chromosome Type of amyloid Disorder
21 β-amyloid Familial Alzheimer disease, Down syndrome, hereditary cerebral hemorrhage with amyloid angiopathy (Dutch, Italian, Flemish, Iowa, Piedmont, Arctic types)
20 AC peptide (precursor – cystatin C) Hereditary cerebral hemorrhage with amyloid angiopathy Icelandic type
PrPSc peptide (precursor – prion protein) Gerstmann-Straussler-Scheinker disease
18 ATTR peptide (precursor – protein transthyretin) Cerebral transthyretin-associated amyloid angiopathy
13 ABri peptide Familial British dementia
ADan peptide Familial Danish dementia
9 AGel peptide (precursor -protein gelsolin) Finnish type of familial amyloidosis

 

Symptoms


Symptoms of CAA are related to the  following conditions which occur as a result of CAA:

  • Transient neurologic events may occur as the prodromes for hemorrhages characterized by the temporal focal muscle weakness, paralysis, paresthesias, or numbness sometimes accompanied by the episodes of confusion or seizures;
  • Intracerebral hemorrhages, lobular cortical hemorrhages, and focal convexity subarachnoid hemorrhages are characterized by the drowsiness, headache (may be localized in one part of the head), confusion, vision and perception impairment, speech difficulties, muscle weakness or paralysis (depending on the lesion localization), seizures (usually partial), nausea and vomiting, impaired coscioussness or coma. Headache localization may indicate the injured part of the brain: 1) headache in the frontal part of the head – lesion in the frontal lobe; 2) one-side parietal headache – parietal lobe is affected; 3) eye and ear pain on the same side of the head – temporal lobe is damaged; 4) eye pain on the same side of the head – lesion is located in the occipital lobe;
  • Dementia is characterized by the impaired cognitive functions and usually develops as Alzheimer disease. CAA is observed in up to 80-85% of cases of Alzheimer disease;
  • CAA-related inflammation commonly appears as subacute reversible leukoencephalopathy;

Less commonly CAA may result in ischemic strokes, dementia with spasticity and ataxia, vascular malformations, etc.

See also: Amyloidosis


Diagnosis


To verify the diagnosis a brain sample is needed. Usually the diagnosis is made after the autopsy.

However, in some cases increased β-amyloid or ApoE may be found in the cerebrospinal fluid. CT, MRI and PET scans are performed to verify the lesion localization. Angiography may also be required.

The CAA diagnosis is made based on Boston criteria for cerebral amyloid angiopathy.

 

Treatment

There is no cure for CAA, so the management of the disease is usually symptomatic. Intracranial hemorrhages may be life-threatening and require medical attention.

Rehabilitation and speech therapy are necessary to increase the quality of person’s life.

 

Applicable medicines

Long-term treatment with corticosteroids or cyclophosphamide is indicated when the brain vessels are inflamed (vasculitis or perivascular inflammation).

Cerebril (Neurochem, Inc) is a drug supposed to decrease amyloid formation and deposition. However, there are no studies of its administration for CAA.

A recent study showed that antihypertensive medicine perindopril is able to reduce the risk of CAA-related intracranial hemorrhage.

Anti-seizure drugs my also be prescribed.

Amyloidosis test