This paper deals with the question of whether small blood vessel damage is a primary factor in the pathogenesis of AD, an idea advanced years ago that has since been eclipsed by the deluge of experimental data that incriminates amyloid aggregates as the major toxins that act directly on neurons. But the tide is turning back to vascular hypoperfusion and ischemia as causative factors that act in collaboration with amyloid to damage blood vessels and inflict the pain of hypoxia on the neighboring neurons.

The advance in this paper is the technology that allows researchers to watch in real time the development of blood vessel damage in living animals, a very important and much needed technology. The most interesting finding is the observation that vessel damage in the Arctic/Swedish APP mouse occurs globally throughout the entire microvasculature of the brain. It is interesting to note that the image showing diffuse vascular damage in the mouse brain (Fig. 2) looks remarkably similar to the distribution of vascular damage in elderly human AD brains (Fig. 2, Buée et al., 1994).

References:
Buée L, Hof PR, Bouras C, Delacourte A, Perl DP, Morrison JH, Fillit HM. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol. 1994;87(5):469-80. Abstract

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