New research suggests that accumulation of amyloid-â peptides in cerebral blood vessels, as opposed to the brain itself, may be a more important pathological mediator of Alzheimer's disease. Two independent yet related articles describe such findings in the August issue of The American Journal of Pathology.
Alzheimer's disease, the most common form of progressive dementia, affects an estimated 4.5 million Americans according to the Alzheimer's Association. Amyloid-â (Aâ) deposition is a hallmark of Alzheimer's disease and other cerebral amyloid angiopathies. However, exactly how Aâ accumulates and causes damage is not fully understood.
In the first article, "Cerebral microvascular Aâ deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant AâPP," Miao et al. describe early-onset Aâ deposition in Tg-SwDI mice. These mice express Aâ protein with mutations that are found in human early-onset cerebral amyloid angiopathy, causing specific accumulation of Aâ in cerebral blood vessels.
The Aâ peptides accumulated because they could not adequately cross the blood-brain barrier to be cleared from the brain. Over time, Aâ accumulation increased in the cerebral microvessels of the thalamus and subiculum of the brain. This resulted in degeneration of blood vessels as evidenced by reduced vessel density and increased apoptosis. Neuroinflammation also occurred as large numbers of microglia, along with inflammatory cytokines, were found at sites of Aâ accumulation.
The authors conclude that early-onset Aâ accumulation occurs predominantly in the cerebral microvasculature and appears largely responsible for the neuroinflammation in these mice. They also demonstrate the utility of Tg-SwDI mice in studying cerebral amyloid angiopathies, such as Alzheimer's disease.
The second article, by Kumar-Singh et al., "Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls," utilizes two different transgenic mice: Tg2576 and PSAPP. Both models produce dense-core plaques, highly concentrated deposits of Aâ, and were used to investigate the possible association of blood vessels with Aâ deposits.