I have been a longtime admirer of Thomas Krucker’s vascular corrosion casting studies in mice, which resemble a 3-D micro-CT scan but are much more detailed and analyzable. They are especially useful when combined with magnetic resonance angiography imaging. In the present study, Krucker and his colleagues reveal changes observed in the cerebrovascular architecture of APP23 tg mice who were followed in an age-dependent time period lasting 25 months. During that time, parenchymal amyloid plaques appeared in the transgenic group, but only following significant microvascular changes. The slowly evolving microvascular pathology prior to plaque formation that the authors observed in the APP23 mice indicated to them that the disrupted microvessels ostensibly contribute to the early memory/learning deficits seen in this transgenic mouse model. The authors further conclude that early damage in the tg microvessels may worsen progressively over time, and could reflect the actual pathogenesis of AD, a point we have argued for many years (1).
These experimental observations confirm, and...
The authors investigated the vascular alterations occurring in a
mouse model of Alzheimer disease (AD) using corrosion casts and
scanning electron microscopy. They report that APP23 mice exhibit
structural alterations in cerebral microvessels before full-blown
amyloid plaque deposition occurs. These alterations include formation
of perivascular microdeposits, distortion, and remodeling of cerebral
microvessels. As the accumulation of amyloid progresses, there are
areas of loss of blood vessels that correspond to amyloid deposits
and are surrounded by a halo of increased vascularization.
These observations provide a striking demonstration of the severe
microvascular disruption in APP23 mice that develop well before the
onset of cognitive decline. These highly restricted microvascular
alterations fit well with the disruption in cerebrovascular
regulation reported in APP mice. APP mice exhibit severe reduction
in functional hyperemia, a vital homeostatic mechanism that matches
local energy requirements with blood flow, and in the ability of
cerebral microvessels to vasodilate...