Figure 1.

Spine density in vivo is maintained in normal aging but decreased in aged Tg2576 cortex. Examples of spiny dendrites (arrows) and aspiny processes (arrowheads) filled with GFP (green) are presented in control cortex (A), 8- to 10-month-old Tg2576 cortex (B), and 18- to 24-month-old Tg2576 cortex (C). Vasculature is labeled with Texas Red. Aspiny processes are more often associated with plaques (blue). D: Spiny dendrites in nontransgenic animals have 0.284 ± 0.123 spines/μm at 8 to 10 months of age and 0.296 ± 0.111 spines/μm at 18 to 24 months, showing maintenance of spine density with normal aging. In Tg2576 mice, there is no significant loss of spines at 8 to 10 months, before amyloid deposits are common in the cortex. At 18 to 24 months, dendritic spine density is significantly lower within 50 μm of plaques (Tg2576 < 50) and distant from plaques (Tg2576 > 50). E: At 8 to 10 months in Tg2576 cortex, there are already more aspiny neurites present than in control animals. At 18 to 24 months, the proportion of aspiny neurons is increased with a more pronounced effect near plaques, indicating that many previously spiny dendrites have been stripped of spines. F: Because only spiny processes were used to determine spine density, the loss of spine density in (D) is probably an underestimate. Taking into account the proportion of neurites that have lost their spines, spine loss is even more pronounced in Tg2576 cortex (see Results for discussion). *P < 0.05. Bonferroni-Dunn post hoc tests; ^#P < 0.05. χ² P values from contingency analysis. Data are presented as mean ± SD. Scale bar = 10 μm.