Relations between phonological processing abilities and word-level reading skills were examined in a longitudinal correlational study of 216 children. Phonological processing abilities, word-level reading skills, and vocabulary were assessed annually from kindergarten through 4th grade, as the children developed from beginning to skilled readers. Individual differences in phonological awareness were related to subsequent individual differences in word-level reading for every time period examined. Individual differences in serial naming and vocabulary were related to subsequent individual differences in word-level reading initially, but these relations faded with development. Individual differences in letter-name knowledge were related to subsequent individual differences in phonological awareness and serial naming, but there were no relations between individual differences in wordlevel reading and any subsequent phonological processing ability.Phonological processing refers to using the phonological or sound structure of oral language when one processes oral and written language (Jorm & Share, 1983; Wagner & Torgesen, 1987). Spoken words represent combinations of basic sounds or phonemes. In English, for example, there are roughly 30 to 45 basic phonemes, depending on the classification system that is used. Of the nearly infinite number of possible combinations of phonemes, only a relatively small number actually occur, and most combinations of phonemes occur in multiple words. Thus, bat and cat each contain 3 phonemes, the latter 2 of which are shared. This fact is represented by their spellings, which have different initial letters and identical medial and final letters because the spellings in alphabetic orthographies such as English represent sound as well as meaning.Developmental and individual differences in phonological processing abilities appear to be related to the acquisition of reading skills, although the direction, magnitudes, and underlying mechanisms responsible for such relations have yet to be

The receptor for advanced glycation end products (RAGE) is thought to be a primary transporter of beta-amyloid across the blood-brain barrier (BBB) into the brain from the systemic circulation, while the low-density lipoprotein receptor-related protein (LRP)-1 mediates transport of beta-amyloid out of the brain. To determine whether there are Alzheimer's disease (AD)-related changes in these BBB-associated beta-amyloid receptors, we studied RAGE, LRP-1, and beta-amyloid in human elderly control and AD hippocampi. In control hippocampi, there was robust RAGE immunoreactivity in neurons, whereas microvascular staining was barely detectable. LRP-1 staining, in contrast, was clearly evident within microvessels but only weakly stained neurons. In AD cases, neuronal RAGE immunoreactivity was significantly decreased. An unexpected finding was the strongly positive microvascular RAGE immunoreactivity. No evidence for colocalization of RAGE and beta-amyloid was seen within either microvessels or senile plaques. A reversed pattern was evident for LRP-1 in AD. There was very strong staining for LRP-1 in neurons, with minimal microvascular staining. Unlike RAGE, colocalization of LRP-1 and beta-amyloid was clearly present within senile plaques but not microvessels. Western blot analysis revealed a much higher concentration of RAGE protein in AD hippocampi as compared with controls. Concentration of LRP-1 was increased in AD hippocampi, likely secondary to its colocalization with senile plaques. These data confirm that AD is associated with changes in the relative distribution of RAGE and LRP-1 receptors in human hippocampus. They also suggest that the proportion of amyloid within the brains of AD patients that is derived from the systemic circulation may be significant.

Reduced clearance of amyloid β peptides (Aβ) across the blood-brain barrier contributes to amyloid accumulation in Alzheimer disease. Amyloid β efflux transport is via the endothelial low-density lipoprotein receptor-related protein 1 (LRP-1) and P-glycoprotein (P-gp), whereas Aβ influx transport is via the receptor for advanced glycation end products. Because age is the major risk factor for developing Alzheimer disease, we measured LRP-1 and P-gp expression and associated transporter expression with Aβ accumulation in aging rats. Quantitative LRP-1 and P-gp microvessel expression was measured by immunohistochemistry (IHC); LRP-1 and P-gp expression were assessed in microvessel isolates by Western blotting. There was an age-dependent loss of capillary LRP-1 across all ages (3-36 months) by IHC (linear trend p = 0.0004) and between 3 and 20 months by Western blotting (linear trend p < 0.0001). There was a late (30-36 months) P-gp expression loss by IHC (p < 0.05) and Western blotting (p = 0.0112). Loss of LRP-1 correlated with Aβ42 accumulation (p = 0.0121) and very nearly with Aβ40 (p = 0.0599) across all ages. Expression of LRP-1 correlated negatively with the expression of receptor for advanced glycation end products (p < 0.0004). These data indicate that alterations in LRP-1 and P-gp expression seem to contribute progressively to Aβ accumulation in aging.