Amyloid Angiopathy

The deposition of amyloid in the wall of cerebral blood vessels is a well-documented change found in physiological and pathological (AD) aging of the human brain. Amyloid fibrils are deposited extracellularly and are derived from soluble circulating proteins that have undergone partial proteolysis and polymerization resulting in insoluble aggregates. Different components take part in the final composition of amyloid deposits and include, in addition to the straight, nonbranching protein fibrils (diameter: 7-10 nm), a serum glycoprotein (P-component) showing a structural homology with c-reactive protein (an acute phase reactant) and sulphated proteoglycans. Since amyloid fibrils have an affinity for Congo red stain, show a green birefringence in polarized light and a ^-plated sheet pattern at X-ray diffraction analysis, they have been reliably identified and precisely localized in selected areas of the brain tissue. The favorite sites of amyloid deposition are the outer surface of the endothelial basement membrane of the capillaries, the basement membrane of pericytes, and the basement membrane surrounding the smooth muscle cells of veins and arteries (see Figure 40.1).

The basement membranes of astrocytes surrounding the perivascular space are also favorite sites of amyloid deposition. Not all regions are affected by amyloid angiopathy, but capillaries, veins, and arteries may be involved. White matter is reported to be free of amyloid deposits, whereas gray matter regions (cerebral and cerebellar cortex) and leptomeninges may show consistent amyloid angiopathy with advancing age. The progressive accumulation of amyloid around capillaries results in the occlusion of lumen; the same process affecting the smooth muscle cells of arteries and veins leads to degenerative alterations and necrotic lesions of the tunica media of the blood vessel wall, and, as a consequence, the formation of small aneurysms, focal thrombosis, and hemorrhages may occur. Amyloid angiopathy is particularly severe in temporal and occipital regions, and in these CNS areas the clinical manifestation of a spontaneous intracerebral mass hemorrhage constitutes the first symptom of a pathological condition (Haan et al., 1994). Specifically in generalized amy-loidoses, amyloidogenic proteins may come from the blood and their deposition begins at the inner surface of the tunica media, whereas in primary cerebral amy-loidoses, the outer side of the same location of the vessel wall is the target of amyloid deposition: a finding supporting that amyloidogenic proteins diffuse from outside into the vessel wall.

More than 30 types of amyloidoses, differentiated according to their location and distribution in the human body, have been classified. With specific reference to brain aging and age-related neurodegenerative diseases, the most common and important is ^A4 amyloidosis. The amyloid precursor protein (APP), a protein spanning the cellular membrane, is secreted by nerve and other types of cells. The spontaneous aggregation of short fragments of APP in the extracellular space is one of the early steps in the formation of insoluble fibrillar amyloid deposits. In the brain, nerve cells and their dendrites are the main sources of APP and are responsible for its metabolism; then APP is transported along the perivas-cular spaces to the subarachnoid space and may deposit in external regions of the blood vessel walls. Although ^A4 amyloid angiopathy may occur without evident clinical signs, it is almost frequently combined with the presence of amyloid deposits, in the form of SP in the cerebral parenchyma (hippocampus, frontal cortex, and amigdala) of AD patients.

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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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