Differences in the cerebral amyloid angiopathy proteome in Alzheimer's disease and mild cognitive impairment.

Cerebral amyloid angiopathy (CAA) is characterized by amyloid beta (Aß) deposition in cerebrovasculature. It is prevalent with aging and Alzheimer's disease (AD), associated with intracerebral hemorrhage, and contributes to cognitive deficits. To better understand molecular mechanisms, CAA(+) and CAA(-) vessels were microdissected from paraffin-embedded autopsy temporal cortex of age-matched Control (n = 10), mild cognitive impairment (MCI; n = 4), and sporadic AD (n = 6) cases, followed by label-free quantitative mass spectrometry. 257 proteins were differentially abundant in CAA(+) vessels compared to neighboring CAA(-) vessels in MCI, and 289 in AD (p < 0.05, fold-change > 1.5). 84 proteins changed in the same direction in both groups, and many changed in the same direction among proteins significant in at least one group (p < 0.0001, R2 = 0.62). In CAA(+) vessels, proteins significantly increased in both AD and MCI were particularly associated with collagen-containing extracellular matrix, while proteins associated with ribonucleoprotein complex were significantly decreased in both AD and MCI. In neighboring CAA(-) vessels, 61 proteins were differentially abundant in MCI, and 112 in AD when compared to Control cases. Increased proteins in CAA(-) vessels were associated with extracellular matrix, external encapsulating structure, and collagen-containing extracellular matrix in MCI; collagen trimer in AD. Twenty two proteins were increased in CAA(-) vessels of both AD and MCI. Comparison of the CAA proteome with published amyloid-plaque proteomic datasets identified many proteins similarly enriched in CAA and plaques, as well as a protein subset hypothesized as preferentially enriched in CAA when compared to plaques. SEMA3G emerged as a CAA specific marker, validated immunohistochemically and with correlation to pathology levels (p < 0.0001; R2 = 0.90). Overall, the CAA(-) vessel proteomes indicated changes in vessel integrity in AD and MCI in the absence of Aß, and the CAA(+) vessel proteome was similar in MCI and AD, which was associated with vascular matrix reorganization, protein translation deficits, and blood brain barrier breakdown.

The perception of three-dimensional cast-shadow structure is dependent on visual awareness.

In the present study we examined whether the perception of depth from cast shadows is dependent on visual awareness using continuous flash suppression (CFS). As a direct measure of how the visual system infers depth from cast shadows, we examined the cast-shadow motion illusion originally reported by Kersten, Knill, Mamassian, and Bulthoff (1996), in which a moving cast shadow induces illusory motion in depth in a physically stationary object. In Experiment 1, we used a disparity defined probe to determine the stereo motion speed required to match the cast-shadow motion illusion for different cast shadow speeds (0°/s-1.6°/s) and different lighting directions. We found that configurations implying light from above produce more compelling illusory effects. We also found that increasing shadow speed monotonically increased the stereo motion speed required to match the illusory motion, which suggests that quantitative depth can be derived from cast shadows when they are in motion. In Experiment 2, we used CFS to suppress the cast shadow from visual awareness. Visual suppression of the cast shadow from awareness greatly diminished the perception of illusory motion in depth. In Experiment 3 we confirmed that while CFS suppresses the cast-shadow motion from awareness, it continues to be processed by the visual system sufficient to generate a significant motion after effect. The results of the present study suggest that cast shadows can greatly contribute to the perception of scene depth structure, through a process that is dependent on the conscious awareness of the cast shadow.